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Objective: This study examined the correlations between receiving care in patient-centered medical home and maternal reports of their mental health and parenting stress in a national sample of mothers of children with autism spectrum disorder (ASD). Method: Participants were 1108 mothers of children with ASD (average age = 10.6 years; 81% male) from the 2011-2012 National Survey of Children’s Health. Multiple linear regression analysis and polynomial logistic regression analysis were used to evaluate if having a child with ASD cared for in a patient-centered medical home was significantly associated with maternal reports of their parenting stress and mental health. We also assessed whether 5 indicators of the American Academy of Pediatrics medical home definition were differentially associated with maternal outcomes. Results: Receiving care in a patient-centered medical home was associated with maternal reports of less parenting stress (standardized β = −0.201; P < .001) and better mental health (odds ratios range from 0.204 to 0.360; P < .001) after controlling for sociodemographic variables. Of the 5 indicators of the medical home definition, only effective care coordination was significantly associated with maternal perceptions of their parenting stress and mental health. Conclusion: Future longitudinal studies are needed to assess the temporal associations between patient-centered medical home status and maternal perceptions of their mental health and parenting stress in mothers of children with ASD.

Background Mothers of children with diabetes are at-risk for experiencing parenting stress and diminished mental/emotional health. To the best of our knowledge, no studies to date have examined whether there are differences in these outcomes between mothers whose diabetic child is managed in a patient-centred medical home or not. Objective The objective of the present study was to assess whether there were differences in mental health and parenting stress among mothers whose diabetic child was managed in a patient-centred medical home or not. Methods Two hundred fifty-three mothers of children with diabetes (mean age = 12.50 years; SD = 3.90) from the 2011–2012 National Survey of Children’s Health were included in this study. Hierarchical multiple regression was conducted to determine the amount of variance that having a patient-centred medical home contributed to maternal emotional/mental health and parenting stress. Results After controlling for child sex, age, race/ethnicity and family poverty level, patient-centred medical home status was associated with better mental health for mothers and less parenting stress. Effective care coordination was the only subcomponent of the patient-centred medical home that significantly contributed to the variance in mother’s mental/emotional health and parenting stress. Conclusions Receiving care in a patient-centred medical home, particularly the care coordination component, may mitigate some of the negative maternal effects of managing a child’s diabetes.

Despite its widespread use, a minimal amount is known regarding the agreement between parent and youth ratings of youth's executive functioning on the Behavior Rating Inventory of Executive Functioning (BRIEF) in typically developing youth. The present study examined parent-child agreement on the BRIEF with a community sample of adolescents and their parents. Ninety-seven parent-child dyads (

Objective Prior twin studies provide support for a single “common factor” that contributes genetic and environmental risk to a range of disordered eating symptoms. However, the common factor may be indexed less well by binge eating (BE) than other symptoms of eating disorders [i.e., body dissatisfaction (BD) and weight preoccupation (WP)]. We sought to explore the presence of a common factor and test whether loadings differed across three key symptoms (i.e., BE, BD, WP). Method Disordered eating was assessed via self-report in 631 female twin pairs from the Michigan State University Twin Registry. Results We detected a common disordered eating factor that was influenced primarily by additive genetic and nonshared environmental influences. However, we observed different loadings on this common factor by symptom type, as factor loadings for BD and WP were stronger than that for BE. Moreover, the residual environmental and/or genetic variances (i.e., those that are independent of the common factor) were larger in BE than those of BD or WP. Discussion Although all three symptoms share a common set of genetic and environmental influences, risk for BE may involve additional genetic, biological, and environmental factors that are not shared with other symptoms of eating pathology. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:157–161)

Pediatric loss of control (LOC) eating is predictive of partial- and full-syndrome binge eating disorder. The interpersonal model proposes that LOC eating is used to cope with negative mood states resulting from interpersonal distress, possibly on a momentary level. We therefore examined temporal associations between interpersonal problems, negative affect, and LOC eating among overweight adolescent girls using ecological momentary assessment (EMA).Thirty overweight and obese (≥85th body mass index (BMI) percentile; BMI: M = 36.13, SD = 7.49 kg/m(2)) adolescent females (Age: M = 14.92, SD = 1.54 y; 60.0% African American) who reported at least two LOC episodes in the past month completed self-report momentary ratings of interpersonal problems, state affect, and LOC eating for 2 weeks. A series of 2-level multilevel models with centering within subjects was conducted.Between- and within-subjects interpersonal problems (p's .05), but not between- (p = .12) or within- (p = .32) subjects negative affect predicted momentary LOC eating. At the between-subjects level, interpersonal problems significantly predicted increases in negative affect (p 001).Naturalistic data lend support to the predictive value of interpersonal problems for LOC eating among adolescents. Interventions targeting interpersonal factors on a momentary basis may be useful during this developmental stage.

Control of gene expression is important to gene therapy for purposes of both dosing and safety. In vivo regulation of gene expression was demonstrated following co-injection of two separate recombinant adeno-associated virus vectors, one encoding an inducible murine erythropoietin transgene and the other a transcriptional activator, directly into the skeletal muscle of adult immunocompetent mice. Transcription was controlled by systemic administration or withdrawal of tetracycline over an 18 week period, demonstrating that the two vectors were capable of transducing the same cell. Cellular or humoral immune responses against the transactivator protein were not detected.

This study examined the relationship between orienting responses to novel events and subsequent exploratory behavior. The N2-P3 electrophysiologic component of the orienting response was found to be larger for novel than repetitive background stimuli. Across subjects, the amplitude of this N2-P3 response in frontal regions strongly predicted the proportional increase in the duration of viewing directed toward novel compared to background stimuli. Within subjects, larger N2-P3 amplitudes in response to novel stimuli were associated with longer viewing durations on those stimuli. These results suggest that the N2-P3 component of the orienting response reflects the activity of a neural system involving frontal networks that dynamically regulates the subsequent allocation of attentional resources to novel stimuli.

Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P = 0.049) or placebo (25%, P < 0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P = 0.009) or placebo (16%, P < 0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P < 0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% Cl 1.5-4.2) and 2.5 times (95% Cl 1.1-2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.

Fluconazole pharmacokinetics were evaluated for 10 volunteers with AIDS who had no clinical evidence of gastroenteritis. Single 100-mg intravenous (i.v.) and oral (p.o.) doses were administered in a randomized, crossover design. i.v. doses were delivered by a constant-rate infusion over 30 min. Serum fluconazole concentrations were measured by gas-liquid chromatography. The i.v. and p.o. studies were modelled simultaneously by iterative two-stage analysis, which provided individual parameter estimates and a population pharmacokinetic model. Median areas under the concentration-time curves for i.v. and p.o. studies did not differ (90.6 and 99.3 micrograms/ml.h, respectively). Consistent with this finding, the median fractional bioavailability was 1.1 (range, 0.45 to 1.3), comparable to those in healthy subjects. Serum pharmacokinetics in these AIDS patients were generally similar to published data for healthy volunteers. However, following p.o. dosing, we observed a slightly delayed and highly variable time to maximum concentration in serum (median, 2 h; range, 15 min to 8 h). Data were well described by a linear, two-compartment pharmacokinetic model with first-order absorption and elimination. Repeated-measures analysis of variance found no significant differences among any of the pharmacokinetic parameters between i.v. and p.o. studies. On the basis of our findings, we suggest no change in dosage of p.o. fluconazole in patients with AIDS who show no clinical signs of enteropathy.

The 2-L polyethylene glycol (PEG) lavage solutions provide efficacy similar to that of standard 4-L PEG formulations in spite of the reduced volume. The comparative efficacy and tolerability of two formulations of 2-L PEG solution remain unknown.To assess the efficacy, safety and tolerability of PEG + Bis compared with PEG + Asc, and to study the effect of bowel cleansing quality on adenoma detection rates.Patients were randomized to receive either 2-L PEG with ascorbic acid (PEG + Asc) or 2-L PEG plus bisacodyl 10 mg (PEG + Bis). The primary endpoint was overall colon cleansing score, assessed by blinded investigators using a validated four-point scale. Secondary endpoints included adenoma detection rate, patient tolerability and compliance and adverse events.Fifty-two patients received PEG + Asc and 55 patients received PEG + Bis. Overall colon cleansing scores (+/-s.d.) were 1.40 +/- 0.69 and 1.75 +/- 0.70 (P0.003) in the PEG + Asc and PEG + Bis groups, respectively. Excellent and good ratings were recorded in 69% and 23% receiving PEG + Asc compared to 38% and 51% (P = 0.01) of patients receiving PEG + Bis. More adenomas were detected in colonoscopies performed with PEG + Asc (39%) than in those performed with PEG + Bis (20%) (P = 0.04). Patient tolerability and safety were similar with both preparations.The use of PEG + Asc resulted in better colon cleansing and higher adenoma detection rates compared with PEG + Bis.

An effective agent is needed that provides rapid onset of sedation and quick recovery for patients undergoing colonoscopy.To assess the efficacy and safety of fospropofol disodium in providing sedation in patients undergoing colonoscopy.A randomized, double-blind, multicentre trial evaluated 127 adult patients who received fospropofol (2, 5, 6.5 or 8 mg/kg) or midazolam 0.02 mg/kg following pre-treatment with fentanyl. Supplemental doses of study medication were allowed to reach a Modified Observer's Assessment of Alertness/Sedation scale scoreor =4. Efficacy end points included sedation success, measures of clinical benefit, sedation, and recovery as well as patient- and doctor-rated satisfaction.Fospropofol produced a significant dose-dependent increase in sedation success from 24% (2 mg/kg), 35% (5 mg/kg) and 69% (6.5 mg/kg) to 96% (8 mg/kg; P0.001). There were also dose-dependent trends for time to sedation, requirements for alternative sedative medication, supplemental doses of sedative and fentanyl, time to ready for discharge and doctor-rated satisfaction scores. Fospropofol was well tolerated, with most adverse events mild-to-moderate in severity.The 6.5 mg/kg dose of fospropofol provides the ideal balance of efficacy and safety for patients undergoing colonoscopy and has been selected for phase 3 clinical development.

Patient compliance with screening recommendations for colorectal cancer remains low, despite a 90% survival rate achieved with early detection. Bowel preparation is a major deterrent for patients undergoing screening colonoscopy. More than half of patients taking polyethylene glycol electrolyte lavage solution and sodium phosphate preparations experience adverse events, such as nausea and abdominal pain. Many adverse events may be associated with dehydration, including rare reports of renal toxicity in patients taking sodium phosphate products. Addressing dehydration-related safety issues through patient screening and education may improve acceptance of bowel preparations, promote compliance and increase the likelihood of a successful procedure.To evidence safety issues associated with bowel preparation are generally related to inadequate hydration.Dehydration-related complications may be avoided through proper patient screening, for example, renal function and comorbid conditions should be considered when choosing an appropriate bowel preparation. In addition, patient education regarding the importance of maintaining adequate hydration before, during and after bowel preparation may promote compliance with fluid volume recommendations and reduce the risk of dehydration-related adverse events.Proper patient screening and rigorous attention by patients and healthcare providers to hydration during bowel preparation may provide a safer, more effective screening colonoscopy.

This study assesses the extent to which women with and without major depression differ by demographic, familial, and occupational characteristics.From a community-based sample, the authors identified 332 women with and 644 women without current or past major depression based on Structured Clinical Interviews for DSM-IV. Demographic and background interviews were conducted in-person.Depressed women were more likely to have gainedor =35 lbs between age 18 and study enrollment (OR=1.6, 95% CI 1.1-2.5), experienced divorce (OR=2.0, 95% CI 1.4-2.8), or changed occupations (OR=1.5, 95% CI 1.1-2.1) compared with non-depressed women. Compared with women with no brothers, those withor =1 brothers were less likely to have a history of depression (OR=0.8, 95% CI 0.6-1.1), whereas compared with women with no sisters, those withor =1 sisters were more likely to have current or past depression (OR=1.4, 95% CI 1.0-1.9). These findings were not influenced by family sibship size.These results illustrate demographic differences between women with and without major depression and that sibship gender rather than size may also influence risk.

Treatment of major depression in menopausal women is controversial. Estrogen replacement therapy (ERT) treats mild depression but may not treat more severe depression in this population. Antidepressants are recommended as treatment for major depression in menopausal women, but the specific efficacy of antidepressants has not been examined in menopause-associated depression. Twenty-two perimenopausal and postmenopausal women aged 40-61 taking stable doses of ERT who met Structured Clinical Interview for DSM-IV (SCID-IV) criteria for major depression were accessioned into an open-label clinical trial of mirtazapine. Subjects were treated with 30-45 mg/day mirtazapine for 8 weeks and were assessed every 2 weeks with the Hamilton Depression Rating Scale-17 (HDRS-17), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) Scale. Remission of depression was defined as an HDRS-17 scoreor =7 at the week 8 study visit. Sixteen (73%) of the enrolled subjects completed the 8-week study. The median HDRS-17 score declined from 20.5 (range 12-37) at baseline to 2 (range 0-9) at week 8 (Wilcoxon signed-rank test, p0.001). Remission of depression was achieved by 14 of 16 (87.5%) study completers. Subjects responded well to mirtazapine regardless of whether their depression preceded ERT use or developed after ERT was initiated. Therapeutic response also appeared independent of menopausal status (perimenopausal vs. postmenopausal), ERT preparation, and concomitant use of medroxyprogesterone. Mirtazapine is an effective treatment for major depression in perimenopausal and postmenopausal women whose depression precedes ERT use and does not respond to ERT or whose depression develops after ERT is initiated.

The N-nitroso-N-methylurea-induced rat mammary tumor model was used to conduct two types of studies: a prevention study designed to test the ability of the novel selective estrogen receptor modulator lasofoxifene (LAS) to inhibit the development of mammary tumors, and a treatment study designed to test the inhibitory effect of LAS on the growth of established tumors. The prevention study indicated that LAS markedly delayed the emergence of N-nitroso-N-methylurea-induced tumors to an extent similar to that obtained by the established antiestrogen tamoxifen (TAM). At the highest dose administered, both TAM and LAS reduced tumor incidence by 75% and total tumor number by 90% relative to the controls. LAS also reduced the multiplicity of tumors, i.e., the mean number of tumors per rat, and resulted in substantially smaller total tumor burden. In the treatment study, LAS significantly inhibited tumor growth compared with the controls. In addition, whereas none of the untreated tumors regressed completely over the experimental period, 40% of LAS-treated tumors regressed by50% at the highest dose (10 mg/kg daily). The results of this study in a rat mammary tumor model indicate that LAS has both chemopreventive and chemotherapeutic effects quantitatively comparable with those of TAM.

The current study examined the anxiolytic effects of cigarette smoking and chewing gum on urge to smoke, withdrawal, and anxiety in response to a public speaking task in 45 undergraduate smokers. Participants were asked to smoke, chew gum, or do nothing in response to the stressor. Participants completed measures of anxiety, withdrawal symptoms, and urge to smoke pre- and poststressor. The smoke group reported fewer urges to smoke pre- and poststressor than the other groups. The smoke and gum groups reported fewer withdrawal symptoms than did the control group poststressor. Chewing gum was helpful in managing levels of withdrawal symptoms compared with the control group. Groups did not differ on measures of anxiety. Results suggest that smoking in response to a stressor may not reduce levels of affective stress. Furthermore, chewing gum may be helpful in managing withdrawal symptoms in response to a stressor.

This study evaluated the concurrent and construct validity of the Child-Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF), a behavior rating scale of children's acute procedural distress and coping, and the coping promoting behaviors and distress promoting behaviors of their parents and the medical personnel who were present in the medical treatment room. Sixty preschool children undergoing immunizations at a county health department served as subjects. Videotapes of the procedures were scored using three observational measures in addition to the CAMPIS-SF. Also, parent, nurse, and child report measures of child distress, fear, pain, and cooperation were obtained. Results indicated that the validity of the CAMPIS-SF codes of Child Coping, Child Distress, Parent Coping Promoting, Parent Distress Promoting, Nurse Coping Promoting, and Nurse Distress Promoting behaviors was supported by multiple significant correlations with the other measures. The interrater reliability of the 5-point CAMPIS-SF scales was good to excellent. The results emphasize that the CAMPIS-SF scales can be used to monitor not only children's acute procedural distress, but also their coping and the various adults' behaviors that significantly influence children's distress. Further, because of the CAMPIS-SF's ease of use, it is likely that the study of the effects of the social environment on children's distress and coping will be facilitated.

Women constitute two-thirds of patients suffering from common depressive disorders. The treatment of depression in women is therefore a substantial public health concern. High-quality, empirical data on depressive disorders specific to women are limited. As a result, there are no comprehensive evidence-based practice guidelines on the best treatment approaches for these illnesses. We conducted a consensus survey of expert opinion on the treatment of 4 depressive conditions specific to women: premenstrual dysphoric disorder (PMDD), depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause.After reviewing the literature and convening a work group of leading experts, we prepared a written survey covering a total of 858 treatment options in 117 specific clinical situations. Depression severity (mild to severe) was specified for most clinical situations. Treatment options included a broad range of pharmacological, psychosocial, and alternative medicine approaches. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. We identified 40 national experts, 36 (90%) of whom completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations.The expert panel reached consensus on 76% of the options, with greater consensus in situations involving severe symptoms. For women with severe symptoms in each of the 4 central disorder areas we asked about, the first-line recommendation was for antidepressant medication combined with other modalities (generally psychotherapy), paralleling existing guidelines for severe depression in general populations. For milder symptoms in each situation, the panel was less uniform in recommending antidepressants. For the initial treatment of milder symptoms, the panel either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (in conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) as a class were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation.The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression in 4 key clinical situations unique to women. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data in comparing modalities with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Various thiol-containing compounds have been shown to inhibit chemically-induced tumors in animal models. Two thiol-containing compounds derived from vegetables, namely 1,2 dithiol-3-thione (DTT) and S-methylmethane thiolsulfonate (MMTS), were tested for their chemopreventive activity in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Each compound was incorporated into the grain-based Teklad 7001 diet and fed to the rats one week prior to initiation with NMU until termination 18 weeks post NMU. DTT was fed at 166 and 500 ppm and MMTS at 200 and 800 ppm. Neither compound exerted a significant inhibitory effect on any index of tumor development including incidence, total tumor, tumor multiplicity, volume or latency. Serum levels of DTT assessed at termination in the 500 ppm DTT group ranged from 10-30 microg/ml. MMTS was undetectable in serum from either MMTS-fed group. The results of this study, using the direct acting carcinogen, NMU, suggest that the chemopreventive effect of thiol-containing compounds may be confined to animal models using carcinogens that require host activation.

Several epidemiological and animal model studies suggest that consumption of olive oil, which is rich in the monounsaturated fatty acid, oleic acid (OA, C18:, n-9) may reduce the risk of breast cancer. There are however, a wide variety of olive oils in the marketplace with levels of OA ranging from a low of 50% to a high of 80% OA. The purpose of this rodent model study was to determine whether the level of OA in olive oil is a key determinant of its protective effects. We compared the inhibitory effects among three different types of olive oil containing 54, 70 and 80% OA and 20, 15 and 5% linoleic acid (LA), respectively, corn oil and a store bought olive oil, using the NMU-induced rat mammary tumor model. While little difference was found in total mammary tumor yields, a differential effect was found in the histological type of tumors formed. Olive oil containing 80% OA and 5% LA exhibited the lowest level of adenocarcinomas and the highest level of the more benign adenocarcinoma arising from within a fibroadenoma. While the reasons for this effect remain to be clarified, these results suggest that future studies on the health benefits of olive oil should take into account the type as well as the amount of olive oil.

The purpose of this study was to examine negative symptoms (NSs) in patients with major depressive disorder (MDD) and their relation to depressive symptoms (DSs) and other psychiatric symptoms.Features similar to NSs were previously described in patients with depression.The Hamilton Rating Scale for Depression (HRSD), Positive and Negative Symptom Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), and Mini-Mental State Examination were administered to 23 patients with MDD and 10 normal control subjects.As expected, the mean scores of the HRSD, SANS, and negative symptom subscale of the PANSS of the patients with MDD were significantly higher than those of control subjects, validating the clinical significance of NSs as well as DSs in MDD patients. Within the MDD group, although measures of NSs were intercorrelated, there were no other correlations between the measures. Thus, measures of NSs and DSs were not intercorrelated. When the HRSD was divided in two subscales, HRSD negative symptom subscale scores but not HRSD depressive symptom subscale scores were correlated with PANSS negative symptom subscale and SANS total scores as well as with scores on the affective flattening subscale.These results suggest a high level of NSs in patients with MDD, which are distinct from positive symptoms of depression and may constitute a distinct dimension. Negative symptoms and DSs in MDD may represent separate constructs. Further, the HRSD might have possible subscales in MDD as it does in schizophrenia.

Six experiments examined infants' ability to associate nonsense words with 2 causal actions: pushing and pulling. Although Experiment 1 found that 14-month-olds failed to form word-action associations, 18-month-olds in Experiment 2 provided reliable evidence of doing so. Additional experiments explored why 14-month-olds may not have formed such an association. Experiment 3 examined 14-month-olds' ability to discriminate a change in either the action or the label when the other element was held constant. Infants discriminated the change in label but not the change in action. When the language labels were replaced with music (Experiments 4-6), 14-month-old infants responded in terms of and discriminated between pushing and pulling. These results, in comparison with those from Experiments 1 and 3, suggest that for 14 month-olds, attempting to associate labels with actions may interfere with their discrimination of similar actions.

Hybrid Polar Cytodifferentiation (HPC) agents represent a novel class of anticancer compounds which act by inducing terminal differentiation and/or apoptosis rather than by cytotoxic action. Among these are HPC agents such as hexamethylenebisacetamide (HMBA) and more potent 2nd generation hybrid/polar compounds such as suberanilohydroxamic acid (SAHA). As of the present, most studies on HPC agents have focused on cancers of the hematopoietic system rather than solid epithelial tumors. The objective of the present study therefore was to assess the chemopreventive action of these two related compounds in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Female Sprague-Dawley rats were fed diets containing 450 and 900 ppm, SAHA and 1000 and 2000 ppm HMBA, starting one week prior to NMU administration and continued for a period of 18 weeks. Mammary tumor development was monitored by palpation throughout the study, and at termination tumor incidence, number, multiplicity, latency and volume were determined. Weight gain was measured biweekly throughout the study. The salient results were as follows: SAHA at 900 ppm reduced NMU-induced mammary tumor incidence by 40%, total tumors by 66%, mean tumor multiplicity by 43% and mean tumor volume by 78%, with no detectable toxic side effects. HMBA exerted no tumor inhibiting effects at either concentration. This study represents the first demonstration that an HPC agent, namely SAHA, can inhibit the development of a chemically-induced, solid, epithelial tumor, at a relatively low dose (approximately 13 mgs/rat/day) without untoward side effects.

The Fiber Hypothesis which had its origins in the work of Burkitt and others in the early 1970's, focussed largely on fiber's beneficial effects on colon cancer and disorders of the gastric intestinal tract. In the 1980's it was proposed that fiber may also have beneficial effects on breast cancer and a rational for this was proposed involving modulation, by fiber, of the enterohepatic recirculation of estrogens. In the following the evidence from epidemiology, clinical interventions and animal model studies, supporting a role for fiber in breast cancer is critically reviewed. Evidence from animal model studies support the notion that supplementary fiber inhibits chemically-induced mammary tumorigenesis but do not support an estrogen-based mechanism. Some studies in human populations suggest modulation by estrogens and some do not. The aggregate data point to minor constituents present in fiber, such as isoflavones and phytate as the biologically active components of fiber which may be responsible for its anti cancer effects.

Epidemiological and experimental studies suggest that consumption of garlic may protect against several types of cancer. Moreover, a plausible hypothesis has been proposed that the biological effects of garlic can be attributed to the enhancing action of a variety of organosulfur compounds, present in garlic, on hepatic phase II carcinogen detoxification enzymes. We have used the N-methylnitrosourea (NMU)-induced rat mammary tumor model to test the chemopreventive effects of a water-soluble organosulfur constituent derived from aged garlic, S-allylcysteine (SAC). Rats were fed diets supplemented with 666 and 2,000 ppm SAC beginning seven days before initiation with NMU (55 days of age) to termination (18 wk post-NMU), at which time mammary tumors were enumerated. At neither dose did SAC exert an inhibitory effect on any index of tumor development, including incidence, latency, multiplicity, or volume, compared with untreated controls. Weight gains in all groups were similar. Assay of serum SAC levels in supplemented groups indicated that SAC concentrations were beneath the limits of detection of the high-performance liquid chromatography system used. These results contradict previous animal model studies indicating that SAC acts as an inhibitory agent in experimental mammary tumorigenesis; reasons for this discrepancy include the possibility that SAC may exhibit nonlinear dose effects.

This study compared distraction, an anesthetic (eutectic mixture of local anesthetics [EMLA]), and typical care during pediatric immunizations. Participants were 39 4th graders receiving a 3-injection vaccination series over a 6-month period. Children displayed low distress despite reporting moderate anxiety and pain. Distraction resulted in more nurse coaching and child coping and less child distress than did EMLA or typical care on an observational measure. EMLA did not result in increased child coping or decreased distress. In fact, the nurse coached more, and trends suggested that children coped more with typical care than with EMLA. Whereas participant ratings and heart rate did not differ among conditions, all 3 conditions demonstrated improvements over time with these measures. Satisfaction ratings suggested that children preferred the treatments to typical care, whereas the nurse appreciated aspects of each of the conditions. Finally, distraction was more economical than EMLA.

In a previous study, Wrigley's chewing gum was shown to reduce cravings to smoke and nicotine withdrawal when smokers were not allowed access to cigarettes. The present study expanded these findings by examining smoking behavior of 20 dependent cigarette smokers who were allowed free access to cigarettes throughout the study session but were encouraged and rewarded not to smoke. Each experimental session consisted of the participant watching a movie, then waiting an additional 30 min. Half of the participants were assigned to a gum condition in which they were asked to chew at least one piece of gum and had free access to chewing gum throughout the experimental session; half were assigned to a no-gum control. Results from this study indicate that when gum was present, participants took significantly fewer puffs and abstained for a longer period of time until their first cigarette. These results suggest that chewing gum may facilitate quit attempts.

The authors examined the influence of neuroticism (N) on the occurrence of different types of daily events, primary and secondary appraisals of those events, use of specific coping strategies, and end-of-day negative mood. College students completed questionnaires at the end of every day for 14 consecutive days. When reporting their most stressful event of each day, high-N individuals, compared with low-N individuals, reported more interpersonal stressors and had more negative primary and secondary appraisals and reacted with more distress in response to increasingly negative primary and secondary appraisals. Compared with low-N individuals, high-N individuals used less-adaptive coping strategies (e.g., hostile reaction) and reacted with more distress in response to some types of coping strategies. The appraisal findings, in particular, help to explain the chronic negative affectivity associated with neuroticism.

To better understand apathy and disengagement in patients with Alzheimer's disease (AD), the authors investigated possible behavioral mechanisms underlying diminished novelty-seeking activity in patients with probable AD.Apathy and disengagement have been shown to be the most common behavioral changes associated with AD.Patients and age-matched normal controls had their eye movements recorded while pairs of line drawings pitting an incongruous figure against a congruous figure were shown on a screen for 12 seconds. Characteristics of a subset of AD patients who were indifferent to novel visual stimuli as measured by exploratory eye movements were compared to those of a subset of AD patients who were attracted to novel stimuli to a degree similar to that of normal controls.The indifferent patients were judged by informants, who completed a personality questionnaire, to exhibit a greater degree of apathy. The two AD groups did not differ in overall dementia severity or performance on a Saccade-to-Target Task that required shifts of attention and gaze. In a separate task, the indifferent patients were able to accurately identify the more novel stimuli in 97.5% of trials. Normal control subjects exhibited a strong bias toward processing novel stimuli, directing a higher proportion of their first fixations and dwell time to the incongruous stimuli whether the analysis was run for 3, 6, or 12 seconds of viewing. Indifferent patients did not direct their initial fixation toward novel stimuli and distributed their looking time evenly between incongruous and congruous stimuli throughout all measured intervals.The results suggest that the indifference to novelty observed in some patients with probable AD cannot simply be attributed to global cognitive decline, more elementary attentional deficits, more rapid habituation of response to novel stimuli, or an inability to discriminate upon demand between stimuli of varying degrees of novelty. It is more likely that their behavior reflects a disruption, by AD pathology, of neural systems that modulate behavioral engagement and maintain attentional bias toward novel events in the environment.

Studies in laboratory animals and epidemiological surveys suggest a relationship between the type and amount of dietary fat and mammary cancer. One mechanism proposed to explain this relationship is modulation by dietary fat, of mammary tumor eicosanoid levels through action at the rate limiting enzyme in eicosanoid synthesis, cyclooxygenase (COX). Until recently there have been no studies which have examined COX gene expression in human breast or rodent mammary tissues. In this study we have demonstrated the presence of two immunoreactive isoforms of cyclooxygenase (COX-1 and -2), and the modulating effects of n-3 fatty acids on their expression, in N-nitrosomethylurea (NMU)-induced rat mammary tumors. Three different high fat diets were compared namely, corn oil (CO) 23%; CO 18% menhaden oil (MO) 5%; CO, 5%/MO 18%; low fat corn oil (5%) served as a control. It was found that immunoreactive COX-2 protein levels were approximately 3x higher than COX-1 levels in NMU-induced mammary tumors. Moreover, the high menhaden oil diet (rich in n-3 fatty acids) significantly suppressed both COX-1 (-28%) and COX-2 (-36%) protein levels when compared to the high corn oil diet. No differences were found among the other treatment groups when compared pair-wise or with low-fat control. The mechanism(s) by which n-3 fatty acids suppress COX-1 and COX-2 remain to be determined.

The following experiments were designed to determine the age at which infants can first readily learn word--object pairings with only minimal exposure and without social or contextual support. To address this question, 8- to 14-month-old infants were tested on their ability to form word--object associations in a "switch" design. Infants were habituated to 2 word--object pairings and then tested with 1 trial that maintained a familiar word--object pairing and 1 that involved a familiar word and object in a new combination. Across 6 experiments, only 14-month-old infants formed word--object associations under these controlled testing conditions but appeared to do so only when the objects were moving. Although 8- to 12-month-olds did not form the associations, they appeared to process both the word and the object information. These studies provide strong evidence that 14-month-old infants can rapidly learn arbitrary associations between words and objects, that this ability appears to develop at about 14 months of age, and that the Switch design is a useful method for assessing word--object learning in infancy.

Although the postpartum period has typically been considered a period of risk for relapse of bipolar disorder, systematic data regarding the course of bipolar disorder during pregnancy is essentially unknown. The management of bipolar women who plan to conceive or who are pregnant poses significant challenges for clinicians who care for these patients. Recent data suggest that pregnancy is not protective and the risk for relapse after lithium discontinuation is similar in pregnant and nonpregnant women with 50 percent relapsing within 6 months. This article reviews the major clinical dilemmas in managing pregnant bipolar patients and recent data on the course of bipolar disorder during pregnancy. Treatment guidelines are presented.

Individuals who lack the ability to pay for dental care or who do not have an ongoing relationship with a private practice dentist may use hospital emergency rooms (ERs) for dental treatment. The purpose of this study was to analyze patterns of ER use for the treatment of dental conditions by day of week and time of day, and contrast this with similar patterns of use of ERs for the treatment of medical conditions. Results of this study indicate that, while medical visits are evenly distributed during the week, dental visits are most numerous on Saturday and Sunday. In addition, while medical ER visits are highest during 9 a.m. to 5 p.m. and lowest during 12 a.m. to 6 a.m., dental visits are highest during 5 p.m. to 9 p.m. and lowest during 6 a.m. to 9 a.m.

Although psychotropic drugs have not been tested or approved by the Food and Drug Administration for use during pregnancy, some women continue to take these medications while they are pregnant, particularly since mood and anxiety disorders cluster in women during childbearing years. The relative risks and benefits of drug therapy for these women must be weighed with each patient and treatment limited to those situations in which risks to mother and fetus from the disorder are presumed to exceed the risk of drug treatment. Risks of psychotropic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer term neurobehavioral sequelae. Of growing concern is the risk of untreated psychiatric disorder as it may potentially affect fetoplacental integrity and fetal central nervous system development. Coordination of care with the patient, her husband or partner, and the obstetrician is essential, as is careful medical record documentation when treating pregnant patients with psychiatric disorders.

Mood disturbance occurs commonly during the postpartum period. The symptoms may be transient and relatively mild (as in postpartum blues) or may be associated with significant impairment of functioning (as in postpartum depression and puerperal psychosis). Despite the prevalence of postpartum mood disorders, depressive symptoms that emerge during the puerperium are often overlooked. Puerperal affective illness places the mother at risk for the development of recurrent depression and has also been associated with significant long-term effects on child development and behavior. Therefore, the prompt recognition and efficacious treatment of puerperal mood disorders are essential in order to avoid adverse outcomes for both mother and infant. This article discusses the evaluation of postpartum mood disturbance and offers guidelines for the treatment of affective illness during the puerperium.

Because the onset of mood and anxiety disorders often occurs during the childbearing years, many women may be taking psychotropic medications for these disorders when they conceive. These medications easily diffuse across the placenta, and their impact on the fetus is of concern. But discontinuation may lead to relapse, in which case psychiatric symptoms may affect the fetus. Thoughtful treatment planning presents a dilemma to the clinician. Limited data suggest heightened vulnerability to relapse of mood and anxiety disorders in women during the postpartum period. Pregnancy appears to exacerbate symptoms of obsessive-compulsive disorder, while panic disorder patients may remain well after discontinuing medication. Future studies should address the prevalence and relapse rates of mood and anxiety disorders, particularly after medication discontinuation, among pregnant women.

We reviewed 61 patients seen from 1975 to 1994 with a biopsy-confirmed optic chiasm astrocytoma or a characteristic clinical and imaging presentation. The mean age at diagnosis was 72 months, including 30 who were less than 5 years old. The mean tumor diameter at presentation was 31 mm among 54 tumors measured. Tumors involved the optic nerve in 41, hypothalamus in 38, optic tract in 15, and optic radiations in 2. Four patients, all with neurofibromatosis, received no treatment. Forty patients received conventional radiation therapy at a mean age of 89 months. Chemotherapy was given to 19 children and 7 of these were followed for greater than 1 year. Six of these 7 had progressive disease which required subsequent surgery and/or radiation therapy. Thirty-six patients underwent surgery. We restricted our analysis of outcome to those 38 patients followed for longer than 60 months. Development was normal in 13%, mildly disabled in 53%, severely disabled in 21% and dead in 13%. Children were severely disabled or dead in 47% if younger than 5 years at diagnosis, and 21% if older. There was no endocrine dysfunction in 18% and new endocrine failure was seen in 61%. More posterior tumors did not portend a poorer prognosis. Children less than 5 years old had a poorer prognosis. Neurofibromatosis did not have a marked effect on outcome. Intracranial hypertension was an indicator of a poor prognosis. No specific treatment modality was clearly superior in terms of long-term survival or improvement in quality of life.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients.

A structured interview was administered to a sample of patients on maintenance dialysis and their attending physicians to obtain information on the documentation of their end-of-life treatment preferences. The majority of the patients reported never having considered stopping dialysis, or having discussed with their nephrologist or family the circumstances in which treatment should be discontinued. Only 7 patients (6%) had completed an advance directive; these patients were all men (P = 0.01) and tended to be better educated (P = 0.02). Only one of the nine physicians had completed an advance directive. In most cases, the dialysis patients and their treatment team staff were preoccupied with the struggles of daily life and had avoided or denied considerations of terminal illness and death. The literature on denial, medical illness, and dying is also reviewed as it relates to dialysis patients, end-of-life treatment, and terminal care.