Yoga's impact on risk and protective factors for disordered eating: a pilot prevention trial.

Yoga has been proposed as a strategy for improving risk and protective factors for eating disorders, but few prevention trials have been conducted. The purpose of this pilot study was to assess the feasibility and acceptability of a yoga series in female college students (n = 52). Participants were randomized to a yoga intervention (three 50-minute yoga classes/week for 10 weeks conducted by certified yoga teachers who received a 3-day intensive training) or a control group. Risk and protective factors, assessed at baseline, 5 and 10 weeks, included body dissatisfaction, negative affect, loneliness, self-compassion, positive affect, and mindfulness. Mixed models controlling for baseline levels of outcome variables were run. On average, participants attended 20 out of 30 yoga classes, and the majority of participants reported high levels of satisfaction with the yoga series. Appearance orientation decreased and positive affect increased in the yoga group relative to the control group. After controlling for baseline levels, the yoga group had a significantly higher positive affect than the control group. Changes in other outcomes were not statistically significant, as compared to the control condition. Future yoga research directions are discussed including education about body image, measure and sample selection, and use of an implementation science framework.

A randomised controlled trial of three psychological treatments for anorexia nervosa.

BACKGROUND: There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy. METHOD: A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25-40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment. RESULTS: Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up. CONCLUSION: The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN 12611000725965) http://www.anzctr.org.au/.

Eating disorder behaviours amongst adolescents: investigating classification, persistence and prospective associations with adverse outcomes using latent class models.

Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity.

Childhood hyperactivity/inattention and eating disturbances predict binge eating in adolescence.

BACKGROUND: Identifying childhood predictors of binge eating and understanding risk mechanisms could help improve prevention and detection efforts. The aim of this study was to examine whether features of attention-deficit/hyperactivity disorder (ADHD), as well as childhood eating disturbances, predicted binge eating later in adolescence. METHOD: We studied specific risk factors for the development of binge eating during mid-adolescence among 7120 males and females from the Avon Longitudinal Study of Parents and Children (ALSPAC), a cohort study of children in the UK, using data from multiple informants to develop structural equation models. Repeated assessment of eating disturbances during childhood (mid-childhood overeating, late-childhood overeating and early-adolescent strong desire for food), as well as teacher- and parent-reported hyperactivity/inattention during mid- and late childhood, were considered as possible predictors of mid-adolescent binge eating. RESULTS: Prevalence of binge eating during mid-adolescence in our sample was 11.6%. The final model of predictors of binge eating during mid-adolescence included direct effects of late-childhood overeating [standardized estimate 0.145, 95% confidence interval (CI) 0.038­0.259, p = 0.009] and early-adolescent strong desire for food (standardized estimate 0.088, 95% CI −0.002 to 0.169, p = 0.05). Hyperactivity/inattention during late childhood indirectly predicted binge eating during mid-adolescence (standardized estimate 0.085, 95% CI 0.007­0.128, p = 0.03) via late-childhood overeating and early-adolescent strong desire for food. CONCLUSIONS: Our findings indicate that early ADHD symptoms, in addition to an overeating phenotype, contribute to risk for adolescent binge eating. These findings lend support to the potential role of hyperactivity/inattention in the development of overeating and binge eating.

Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex).

BACKGROUND: Patient-reported outcome (PRO) questionnaires were recently developed specifically for use with patients with advanced basal cell carcinoma (aBCC) and basal cell carcinoma naevus syndrome (BCCNS). OBJECTIVES: To evaluate the measurement properties of PRO questionnaires for use in patients with aBCC or BCCNS. METHODS: In total 129 patients from 10 clinical sites in the U.S.A. and the BCCNS Support Network completed the two newly developed questionnaires multiple times over 3 months. Patients also completed the Skindex-16 and the 12-Item Short-Form Health Survey as collateral measures. Psychometric properties of the questionnaires were evaluated, including internal consistency and test-retest reliability, construct and known-groups validity, and responsiveness. RESULTS: Based on the results of exploratory factor analysis and clinical input, the two newly developed questionnaires were combined into a single questionnaire, called the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The internal consistency reliability was acceptable, and all aBCCdex scale scores correlated significantly with conceptually similar scales. When divided into groups that differed based on scores from collateral measures, aBCCdex scale scores differentiated between groups (known-groups validity) and were responsive to change. CONCLUSIONS: The aBCCdex is a brief and comprehensive questionnaire appropriate for use with patients with aBCC and BCCNS. Its reliability and validity have been confirmed. Further research is necessary to estimate the minimally important difference in a larger patient population.

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

BACKGROUND: The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). METHOD: Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). RESULTS: Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. CONCLUSIONS: ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

ASAP: A pharmacy-level intervention to increase nonprescription syringe sales to reduce bloodborne illnesses.

BACKGROUND: Pharmacy syringe sales are effective structural interventions to reduce bloodborne illnesses in populations, and are legal in all but two states. Yet evidence indicates reduced syringe sales in recent years. This study was designed as a feasibility test of an intervention to promote syringe sales by pharmacies in Arizona. METHODS: A four-month pilot among three Arizona pharmacies measured feasibility and acceptability through monthly surveys to 18 enrolled pharmacy staff members. RESULTS: Pharmacy staff reported increased ease of dispensing syringes across the study. Rankings of syringe dispensing as 'easiest' among 6 measured pharmacy practices increased from 38.9 % at baseline to 50.1 % post intervention module training, and to 83.3 % at pilot conclusion. The majority (72.2 %) of pharmacy staff agreed that intervention materials were easy to use. Over 70 % indicated that the intervention was influential in their "being more open to selling syringes without a prescription to someone who might use them for illicit drug use," and 61.1 % reported that in the future, they were highly likely to dispense syringes to customers who would use them to inject drugs. A vast majority (92 %) reported being likely to dispense subsidized naloxone if available to their pharmacy at no cost. CONCLUSIONS: An education-based intervention was found to be feasible and acceptable to pharmacy staff and had an observed impact on perceptions of ease and likelihood of dispensing syringes without a prescription to people who may use them to inject drugs.

Treating severe and enduring anorexia nervosa: a randomized controlled trial.

BACKGROUND: There are no evidence-based treatments for severe and enduring anorexia nervosa (SE-AN). This study evaluated the relative efficacy of cognitive behavioral therapy (CBT-AN) and specialist supportive clinical management (SSCM) for adults with SE-AN. METHOD: Sixty-three participants with a diagnosis of AN, who had at least a 7-year illness history, were treated in a multi-site randomized controlled trial (RCT). During 30 out-patient visits spread over 8 months, they received either CBT-AN or SSCM, both modified for SE-AN. Participants were assessed at baseline, end of treatment (EOT), and at 6- and 12-month post-treatment follow-ups. The main outcome measures were quality of life, mood disorder symptoms and social adjustment. Weight, eating disorder (ED) psychopathology, motivation for change and health-care burden were secondary outcomes. RESULTS: Thirty-one participants were randomized to CBT-AN and 32 to SSCM with a retention rate of 85% achieved at the end of the study. At EOT and follow-up, both groups showed significant improvement. There were no differences between treatment groups at EOT. At the 6-month follow-up, CBT-AN participants had higher scores on the Weissman Social Adjustment Scale (WSAS; p = 0.038) and at 12 months they had lower Eating Disorder Examination (EDE) global scores (p = 0.004) and higher readiness for recovery (p = 0.013) compared to SSCM. CONCLUSIONS: Patients with SE-AN can make meaningful improvements with both therapies. Both treatments were acceptable and high retention rates at follow-up were achieved. Between-group differences at follow-up were consistent with the nature of the treatments given.

Daily self-weighing compared with an active control causes greater negative affective lability in emerging adult women: A randomized trial.

Age-related weight gain prevention may reduce population overweight/obesity. Emerging adulthood is a crucial time to act, as rate of gain accelerates and health habits develop. Evidence supports self-weighing (SW) for preventing weight gain; however, how SW impacts psychological states and behaviors in vulnerable groups is unclear. This study assessed daily SW effects on affective lability, stress, weight-related stress, body satisfaction, and weight-control behaviors. Sixty-nine university females (aged 18-22) were randomized to daily SW or temperature-taking (TT) control. Over 2 weeks, participants completed five daily ecological momentary assessments with their intervention behavior. A graph of their data with a trendline was emailed daily, with no other intervention components. Multilevel mixed models with random effect for day assessed variability in positive/negative affect. Generalized linear mixed models assessed outcomes pre- and post-SW or TT and generalized estimating equations assessed weight-control behaviors. Negative affective lability was significantly greater for SW versus TT. While general stress did not differ between groups, weight-related stress was significantly higher and body satisfaction was significantly lower post-behavior for SW but not TT. Groups did not significantly differ in the number or probability of weight-control behaviors. Caution is advised when recommending self-weighing to prevent weight gain for emerging adults.

A latent profile analysis of the typology of bulimic symptoms in an indigenous Pacific population: evidence of cross-cultural variation in phenomenology.

BACKGROUND: Previous efforts to derive empirically based eating disorder (ED) typologies through latent structure modeling have been limited by the ethnic and cultural homogeneity of their study populations and their reliance on DSM-IV ED signs and symptoms as indicator variables. METHOD: Ethnic Fijian schoolgirls (n=523) responded to a self-report battery assessing ED symptoms, herbal purgative use, co-morbid psychopathology, clinical impairment, cultural orientation, and peer influences. Participants who endorsed self-induced vomiting or herbal purgative use in the past 28 days (n=222) were included in a latent profile analysis (LPA) to identify unique subgroups of bulimic symptomatology. RESULTS: LPA identified a bulimia nervosa (BN)-like class (n=86) characterized by high rates of binge eating and self-induced vomiting, and a herbal purgative class (n=136) characterized primarily by the use of indigenous Fijian herbal purgatives. Both ED classes endorsed greater eating pathology and general psychopathology than non-purging participants, and the herbal purgative class endorsed greater clinical impairment than either the BN-like or non-purging participants. Cultural orientation did not differ between the two ED classes. CONCLUSIONS: Including study populations typically under-represented in mental health research and broadening the scope of relevant signs and symptoms in latent structure models may increase the generalizability of ED nosological schemes to encompass greater cultural diversity.

Relationships between symptoms, symptom bother, and health-related quality of life in patients with overactive bladder taking solifenacin or placebo in the VIBRANT study.

AIMS: Studies of antimuscarinics for overactive bladder (OAB) typically use objective and subjective measures to assess efficacy, as each provides unique information about patient outcome. We evaluated the relationships between changes in diary-documented OAB symptoms and other patient-reported outcome (PRO) measures. METHODS: In VIBRANT, OAB patients received solifenacin (5/10 mg) or placebo for 12 weeks. During the study, patients completed 3-day bladder diaries and other generic and disease-specific PRO measures. Data from both treatment groups were combined (n=738). Categorical changes in diary variables were compared with changes in PRO measures. Partial correlations controlling for treatment and Spearman correlations were also calculated. RESULTS: Categorical improvements in diary variables were significantly associated with greater improvements in PRO measures. Pair-wise comparisons showed that patients with major symptomatic improvements had significantly greater improvements on PROs vs. those with some or no improvement. Odds ratios ranged from 1.52 to 4.09 (p≤0.002). Linear relationships between changes in PRO measures and diary variables were low to moderate but statistically significant (p<0.001). Partial correlations were highest for diary variables and OAB-Questionnaire Symptom Bother. Spearman correlations ranged from 0.170 to 0.450 (p<0.001). CONCLUSIONS: In patients with OAB, changes in objectively measured symptoms of urgency, incontinence and frequency showed low-to-moderate correlations to changes in PRO measures. While providing evidence for similar change patterns in symptoms and patient perceptions, correlations were not high, lending support to the concept that in OAB clinical trials, both bladder diaries and PRO measures are important independent measures of efficacy.

Does it fit okay? Problems with condom use as a function of self-reported poor fit.

OBJECTIVE: To identify associations between men's self-reports of ill-fitting condoms and selected condom use problems, using an event-specific analysis. METHODS: A convenience sample of men was recruited via advertisements in newspapers (two urban and one small town) and a blog on the website of a condom sales company. Men completed a questionnaire posted on the website of The Kinsey Institute for Research in Sex, Gender, and Reproduction. Inclusion criteria were: at least 18 years old, used condoms for penile-vaginal intercourse in the past 3 months and the ability to read English. RESULTS: In controlled, event-specific, analyses of 436 men, those reporting ill-fitting condoms (44.7%) were significantly more likely to report breakage (adjusted odds ratio (AOR 2.6), slippage (AOR 2.7), difficulty reaching orgasm, both for their female partners (AOR 1.9) and for themselves (AOR 2.3). In addition, they were more likely to report irritation of the penis (AOR 5.0) and reduced sexual pleasure, both for their female partner (AOR 1.6) and for themselves (AOR 2.4). Furthermore, they were more likely to report that condoms interfered with erection (AOR 2.0), caused erection loss (AOR 2.3), or became dry during sex (AOR 1.9). Finally, they were more likely to report removing condoms before penile-vaginal sex ended (AOR 2.0). CONCLUSIONS: Men and their female sex partners may benefit from public health efforts designed to promote the improved fit of condoms.

How should DSM-V classify eating disorder not otherwise specified (EDNOS) presentations in women with lifetime anorexia or bulimia nervosa?

OBJECTIVE: Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify eating disorder (ED) presentations in individuals who no longer meet full criteria for these disorders. To consider this issue, we examined subthreshold presentations in women with initial diagnoses of AN and BN. METHOD: A total of 246 women with AN or BN were followed for a median of 9 years; weekly symptom data were collected at frequent intervals using the Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations that were subthreshold for 3 months, including those narrowly missing full criteria for AN or BN, along with binge eating disorder (BED) and purging disorder. RESULTS: During follow-up, most women (77.6%) experienced a subthreshold presentation. Subthreshold presentation was related to intake diagnosis (Wald chi2=8.065, df=2, p=0.018). Individuals with AN most often developed subthreshold presentations resembling AN; those with BN were more likely to develop subthreshold BN. Purging disorder was experienced by half of those with BN and one-quarter of those with AN binge/purge type (ANBP); BED occurred in 20% with BN. Transition from AN or BN to most subthreshold types was associated with improved psychosocial functioning (p<0.001). CONCLUSIONS: Subthreshold presentations in women with lifetime AN and BN were common, resembled the initial diagnosis, and were associated with modest improvements in psychosocial functioning. For most with lifetime AN and BN, subthreshold presentations seem to represent part of the course of illness and to fit within the original AN or BN diagnosis.

Is phosphodiesterase type 5 inhibitor use associated with condom breakage?

We tested the hypothesis that phosphodiesterase type 5 inhibitor (PDE5i) use would be associated with increased likelihood of condom breakage using an event-specific analysis. A convenience sample of 440 men completed an internet-based questionnaire that assessed variables pertaining to the last time they used condoms for penile-vaginal intercourse (PVI). A bivariate (screening) analysis was performed to identify covariates for a multivariate analysis using logistic regression. Altogether, 5.9% of the men reported breakage and 9.5% reported PDE5i use during the last time a condom was used for PVI. Among men who had used PDE5i during the last condom-protected occasion of PVI, 11.9% reported breakage compared with 5.3% of those not reporting PDE5i use. Adjusting for men's age, ethnic minority status, marital status, reported duration of PVI and alcohol use at last PVI, those using PDE5i were about four times more likely to also report condom breakage (AOR 4.02; 95% CI 1.20 to 13.48; p = 0.04). Of note, duration of PVI was independently associated with breakage (AOR 1.36; CI 1.02 to 1.83; p = 0.04). Findings suggest that PDE5i use may potentially be associated with increased odds of condom breakage among some men.

Two heads are better than one: the association between condom decision-making and condom use errors and problems.

OBJECTIVES: This exploratory study compared the frequency of condom use errors and problems between men reporting that condom use for penile-vaginal sex was a mutual decision compared with men making the decision unilaterally. METHODS: Nearly 2000 people completed a web-based questionnaire. A sub-sample of 660 men reporting that they last used a condom for penile-vaginal sex (within the past three months) was analysed. Nine condom use errors/problems were assessed. Multivariate analyses controlled for men's age, marital status, and level of experience using condoms. RESULTS: Men's unilateral decision-making was associated with increased odds of removing condoms before sex ended (adjusted odds ratio (AOR) 2.51, p = 0.002), breakage (AOR 3.90, p = 0.037), and slippage during withdrawal (AOR 2.04, p = 0.019). Men's self-reported level of experience using condoms was significantly associated with seven out of nine errors/problems, with those indicating less experience consistently reporting more errors/problems. CONCLUSIONS: Findings suggest that female involvement in the decision to use condoms for penile-vaginal sex may be partly protective against some condom errors/problems. Men's self-reported level of experience using condoms may be a useful indicator of the need for education designed to promote the correct use of condoms. Education programmes may benefit men by urging them to involve their female partner in condom use decisions.

Examining a psychosocial interactive model of binge eating and vomiting in women with bulimia nervosa and subthreshold bulimia nervosa.

The current study tested a psychosocial interactive model of perfectionism, self-efficacy, and weight/shape concern within a sample of women with clinically significant bulimic symptoms, examining how different dimensions of perfectionism operated in the model. Individuals with bulimia nervosa (full diagnostic criteria or subthreshold) completed measures of bulimic symptoms, multidimensional perfectionism, self-efficacy, and weight/shape concern. Among those who were actively binge eating (n=180), weight/shape concern was associated with binge eating frequency in the context of high perfectionism (either maladaptive or adaptive) and low self-efficacy. Among those who were actively vomiting (n=169), weight/shape concern was associated with vomiting frequency only in the context of high adaptive perfectionism and low self-efficacy. These findings provide support for the value of this psychosocial interactive model among actively binge eating and purging samples and for the importance of considering different dimensions of perfectionism in research and treatment related to bulimia nervosa.

Health-related quality of life in randomized controlled trials of lorcaserin for obesity management: what mediates improvement?

Lorcaserin, plus diet and exercise, has demonstrated significant weight loss and improved cardiometabolic parameters vs. placebo in patients with overweight/obesity in three randomized, placebo-controlled trials. We examined whether lorcaserin is also associated with greater improvements in health-related quality of life (HRQOL) and whether these improvements are wholly attributable to weight loss. Pooled data from Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM), Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM) and BLOOM-Diabetes Mellitus (BLOOM-DM) trials were analysed (n = 5624). HRQOL was assessed at baseline and 52 weeks using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Multiple mediation analyses were conducted to evaluate the mechanisms underlying improved HRQOL. Greater HRQOL improvements were observed at 52 weeks in lorcaserin vs. placebo (P < 0.0001). A greater percentage of lorcaserin patients (54.1%) experienced meaningful improvements in IWQOL-Lite total score than placebo patients (48.2%) (P < 0.001). Body mass index (BMI) reduction was the primary driver of improved HRQOL (P < 0.0001), with depressive symptoms and total cholesterol also playing a role (P < 0.05). Improved HRQOL varied by gender, age, race and presence of diabetes and other comorbidities. Lorcaserin treatment significantly improves HRQOL compared with placebo. Although BMI reduction accounts for the majority of these improvements, improvement in depressive symptoms and total cholesterol are contributing factors.

Hematology and clinical chemistry reference values for C57BL/6 X DBA/2 F1 mice.

We have analyzed hematology data from 504 individual male C57BL/6 X DBA/2 (hereafter called B6D2F1) mice. Clinical chemistry data from an additional 304 individual male B6D2F1 mice have also been analyzed. The mice had served as drug-diluent controls in 24 toxicological evaluations of anticancer drugs administered singly or in combination. The studies were carried out under standardized conditions during an 18-month period between July 1975 and December 1976. Test values corresponding to 9 percentiles have been selected from an ordered ranking of values for each of 18 hematologic tests and 18 clinical chemistry tests. Since 95% of the values for a given test are found between the 2.5th and 97.5th percentiles, test values corresponding to these percentiles provide reference values ("normal" values) for these mice. The other percentiles (5th, 10th, 25th, 50th, 75th, 90th, and 95th) indicate the distribution of values between the reference limits for each test. Since values for all tests do not conform to the Gaussian distribution, this nonparametric analysis provides reference values that are more accurate than might be obtained from calculation of the mean and standard deviation of a given test. The B6D2F1 mouse, commonly referred to as BDF1, has been widely used for preclinical evaluation of anticancer drugs, and these data should be useful to investigators who are conducting qualitative and quantitative toxicity evaluations in these mice.

The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer.

The type I receptor tyrosine kinases constitute a family of transmembrane proteins involved in various aspects of cell growth and survival and have been implicated in the initiation and progression of several types of human malignancies. The best characterized of these proteins are the epidermal growth factor receptor (EGFR) and ErbB-2 (HER-2/neu). We have developed potent quinazoline and pyrido-[3,4-d]-pyrimidine small molecules that are dual inhibitors of ErbB-2 and EGFR. The compounds demonstrate potent in vitro inhibition of the ErbB-2 and EGFR kinase domains with IC(50)s <80 nM. Growth of ErbB-2- and EGFR-expressing tumor cell lines is inhibited at concentrations <0.5 microM. Selectivity for tumor cell growth inhibition versus normal human fibroblast growth inhibition ranges from 10- to >75-fold. Tumor growth in mouse s.c. xenograft models of the BT474 and HN5 cell lines is inhibited in a dose-responsive manner using oral doses of 10 and 30 mg/kg twice per day. In addition, the tested compounds caused a reduction of ErbB-2 and EGFR autophosphorylation in tumor fragments from these xenograft models. These data indicate that these compounds have potential use as therapy in the broad population of cancer patients overexpressing ErbB-2 and/or EGFR.