The relationship between global and specific components of quality of life, assessed with the EORTC QLQ-C30 in a sample of 2019 cancer patients.

Quality of life (QoL) is impaired in many cancer patients. The aim of this study was to test whether detriments in QoL were less pronounced in global assessments of QoL compared to more specific components. A total of 2059 cancer patients with mixed diagnoses were examined 6 months after discharge from a cancer rehabilitation clinic. QoL was measured with the EORTC QLQ-C30, which contains a global QoL scale, and 14 functioning and symptom scales and symptom items. A sample of the general population (n = 4476) served as controls. Regression analyses were performed to calculate expected mean scores for the patients, based on their age and gender distribution. Global QoL in the cancer sample (M = 69.3) was nearly equal to that of the general population, while the mean scores of all functioning scales, symptom scales and symptom items showed markedly worse QoL. This general relationship between global and specific QoL was found for seven of eight cancer types. The results indicate that global QoL is not the sum of its parts. This should be considered when treatment effects on QoL are examined. One alternative is to use higher order summarising functioning and symptom scales.

MicroRNAs in acute leukemia: from biological players to clinical contributors.

MicroRNAs (miRNAs) are involved in the management of hematopoiesis. As a consequence, miRNA dysregulation causes disruption of the hematopoietic system and leukemia may arise. We here comprehensively discuss miRNAs found discriminative for cytogenetic and molecular subtypes of acute leukemia. These miRNAs are either known miRNAs involved in leukemogenesis with proven tumor suppressor or oncogenic activities or are newly identified by high-throughput sequencing with yet unknown function. Furthermore, forces are outlined that drive aberrant miRNA function, which include genetic abnormalities (for example, deletions, translocations and mutations) and epigenetic aberrations (for example, aberrant DNA methylation or histone modifications). Interestingly, leukemia-silenced miRNAs can be re-expressed upon treatment with de-methylating agents. Targeting miRNA expression may serve a therapeutical role, albeit at present this way of targeted therapy is in its infancy. However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia.

Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia.

MicroRNAs (miRNAs) relevant to acute lymphoblastic leukemia (ALL) in children are hypothesized to be largely unknown as most miRNAs have been identified in non-leukemic tissues. In order to discover these miRNAs, we applied high-throughput sequencing to pooled fractions of leukemic cells obtained from 89 pediatric cases covering seven well-defined genetic types of ALL and normal hematopoietic cells. This resulted into 78 million small RNA reads representing 554 known, 28 novel and 431 candidate novel miR genes. In all, 153 known, 16 novel and 170 candidate novel mature miRNAs and miRNA-star strands were only expressed in ALL, whereas 140 known, 2 novel and 82 candidate novel mature miRNAs and miRNA-star strands were unique to normal hematopoietic cells. Stem-loop reverse transcriptase (RT)-quantitative PCR analyses confirmed the differential expression of selected mature miRNAs in ALL types and normal cells. Expression of 14 new miRNAs inversely correlated with expression of predicted target genes (-0.49 ≤ Spearman's correlation coefficients (Rs)≤ -0.27, P ≤ 0.05); among others, low levels of novel sol-miR-23 associated with high levels of its predicted (antiapoptotic) target BCL2 (B-cell lymphoma 2) in precursor B-ALL (Rs -0.36, P = 0.007). The identification of >1000 miR genes expressed in different types of ALL forms a comprehensive repository for further functional studies that address the role of miRNAs in the biology of ALL.

Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale.

MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (<1 year) is the most aggressive type of childhood leukemia. To develop more suitable treatment strategies, a firm understanding of the biology underlying this disease is of utmost importance. MLL-rearranged ALL displays a unique gene expression profile, partly explained by erroneous histone modifications. We recently showed that t(4;11)-positive infant ALL is also characterized by pronounced promoter CpG hypermethylation. In this study, we investigated whether this widespread hypermethylation also affected microRNA (miRNA) expression. We identified 11 miRNAs that were downregulated in t(4;11)-positive infant ALL as a consequence of CpG hypermethylation. Seven of these miRNAs were re-activated after exposure to the de-methylating agent Zebularine. Interestingly, five of these miRNAs are associated either with MLL or MLL fusions, and for miR-152 we found both MLL and DNA methyltransferase 1 (DNMT1) as potential targeted genes. Finally, a high degree of methylation of the miR-152 CpG island was strongly correlated with a poor clinical outcome. Our data suggests that inhibitors of methylation have a potential beyond re-expression of hypermethylated protein-coding genes in t(4;11)-positive infant ALL. In this study, we provide additional evidence that they should be tested for their efficacy in MLL-rearranged infant ALL in in vivo models.

Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia.

MicroRNAs (miRNAs) control the expression of protein-coding genes in normal hematopoietic cells and, consequently, aberrant expression may contribute to leukemogenesis. To identify miRNAs relevant to pediatric acute lymphoblastic leukemia (ALL), we cloned 105 known and 8 new miRNA genes expressed in patients' leukemia cells. Instead of known miRNA genes, new miRNA genes were not evolutionarily conserved. Quantification of 19 selected miRNA genes revealed an aberrant expression in ALL as compared with normal CD34+ cells (P

Giant ovarian cysts: is a pre- and intraoperative drainage an advisable procedure?

There has been a considerable debate over the merits of a pre- or intraoperative drainage of giant ovarian cysts, which represented a very frequent approach before definitive surgery in the past. Including our presented case of a 57-year-old woman with a 49 kg mucinous cystadenoma, 19 patients with giant ovarian cysts weighing more than 40 kg were reported in the literature since 1970. An incidence of 37% of malignant and low malignant potential tumors was found. Based on a critical evaluation of the medical courses and the discussed miscellaneous advantages and complications, we conclude that a pre- and intraoperative drainage should be avoided.

Interactions between HIV-infected monocyte-derived macrophages and human brain microvascular endothelial cells result in increased expression of CC chemokines.

The presence of perivascular monocytic infiltration is a major hallmark of HIV-1-associated dementia. Since CC chemokines are chemoattractant cytokines that are able to attract T cells and monocytes/macrophages to sites of inflammation, and since infiltrating monocytes/macrophages remain in close contact with the brain endothelium, we investigated whether interactions between HIV-1-infected macrophages and brain endothelium result in an altered chemokine production. We found an increased mRNA expression of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and RANTES by macrophages after HIV-1 infection. Interactions between HIV-infected macrophages and brain microvascular endothelial cells resulted in an additional upregulation of chemokine mRNA expression, during cell-cell contact as well as in a trans-well system. Since IL-1 beta can function as a modulator of chemokine expression we investigated if interleukin-1 beta could be involved in the regulation of chemokine induction. Coculturing of HIV-infected macrophages and endothelial cells resulted in immune-activation as indicated by increased mRNA expression of IL-1 beta. Subsequently, addition of a neutralizing antibody against IL-1 beta resulted in altered chemokine expression by macrophages, but not by endothelial cells. Thus, IL-1 beta appears to play a major role in the regulation of chemokines during cellular interactions in HIV-associated dementia, but other factors may also be involved.

Development of an instrument to assess readiness to recover in anorexia nervosa.

OBJECTIVE: The degree to which patients with anorexia nervosa demonstrate readiness to recover from their illness has received scant theoretical or empirical attention. Investigating the prevalence and degree of amotivation for recovery in anorexia nervosa, its role in outcome, and the effectiveness of interventions designed to enhance readiness to recover necessitates the existence of a reliable and valid measure of motivational issues relevant to the disorder. The present study aimed to develop and evaluate an instrument for assessing readiness to recover in anorexia nervosa, namely, the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ), a 23-item self-report questionnaire based on Prochaska and DiClemente's stages of change model. METHOD: Seventy-one inpatients with anorexia nervosa participated in the study. On several occasions during their admission, participants completed the ANSOCQ as well as questionnaires assessing readiness to recover, anorexic symptomatology, general distress, and social desirability. RESULTS: The ANSOCQ demonstrated good internal consistency (.90) and 1-week test-retest reliability (.89). Various aspects of validity were also supported, such as significant relationships with other instruments assessing readiness to recover and the prediction of weight gain during different periods of treatment. DISCUSSION: The results suggest that the ANSOCQ is a psychometrically sound instrument that may prove useful in investigating the role of readiness to recover in anorexia nervosa.

Perceived expressed emotion in the siblings and parents of hospitalized patients with anorexia nervosa.

OBJECTIVE: The present study investigated the relationship between the level of perceived Expressed Emotion (EE) of the siblings and parents of patients hospitalized with anorexia nervosa and its effect on weight gain and psychological functioning. METHOD: The Level of Expressed Emotion (LEE) Scale was administered on admission to 19 patients with anorexia nervosa who completed the LEE three times so as to identify their perceptions of their relationship with their closest age sibling, mother, and father. They were also required to complete the Eating Disorder Inventory 2 (EDI-2). Patients' closest age sibling completed the Family Attitude Scale (FAS). The patients' body mass index (BMI) was calculated 6 weeks later, and the EDI-2 readministered. RESULTS: Perceived EE was not predictive of BMI change after 6 weeks of hospitalization. A composite perceived family EE score was a significant predictor of change on the Interpersonal Distrust, Maturity Fears, and Perfectionism subscales of the EDI-2. DISCUSSION: These findings suggest that patients' perceptions of their relationships with their closest aged sibling, mother, and father are poor predictors of weight gain and improvement in psychological functioning following 6 weeks of inpatient treatment.

Paradoxical intention and recursive anxiety.

The present study was designed to investigate a possible relationship between "recursive anxiety" and paradoxical intention. Groups of subjects were chosen from among individuals with public speaking concerns. and for whom fear of fear or recursive anxiety clearly represented an important element, or was completely absent from the clinical profile. These subjects were offered a standard in vivo treatment program for public speaking phobia with inclusion or exclusion of paradoxical intention. A 2 x 2 factorial design was employed. Those whose public speaking anxiety was complicated by recursive anxiety experienced greater improvement when paradoxical intention was included in the treatment program than when it was not employed. In contrast, individuals reporting simple public speaking phobia demonstrated greater success with a treatment program in which paradoxical intention was absent. Wegner's hypothesis of "ironic" cognitive processing was used to explain the proposed relationship between paradoxical intention and fear of fear.

Utility of the functional assessment measure after discharge from inpatient rehabilitation.

OBJECTIVE: To assess the relationship between the Functional Independence Measure (FIM) and the Functional Assessment Measure (FAM), and community integration and return to work in patients with severe traumatic brain injuries (TBI). DESIGN: A cross-sectional, prospective design was used to collect data at 6 and 24 months postdischarge. The Return to Work Scale (RTW) and Community Integration Questionnaire (CIQ) were selected to assess return to work and community functioning. Predictor variables included the motor and cognitive subscales of the FIM and the FAM. SETTING: Follow-up database of an inpatient and community TBI Rehabilitation Unit. PARTICIPANTS: All consenting patients with TBI admitted to the unit, aged 16 or above. There were 88 patients at 6 and 79 patients at 24 month follow-up. RESULTS: At 6 months follow-up, the FAM and the FIM were roughly equivalent in their ability to predict RTW and CIQ scores. At 24 months, FAM motor was the only significant predictor of CIQ, and FAM cognitive scores displayed an advantage over the FIM in predicting employment status. CONCLUSIONS: The FAM subscales produced only modest gains in prediction of employment status and community integration at 24 months postdischarge. This may reflect ceiling effects on the functional measures, a limited range on the RTW measure, poor ecologic validity of functional disability measures in assessing handicap, or a combination of these factors.

Measuring self-esteem in dieting disordered patients: the validity of the Rosenberg and Coopersmith contrasted.

OBJECTIVE: In order to ascertain the most appropriate measure of self-esteem for dieting disordered patients, this study contrasted the construct and convergent validities of two widely used measures. In addition, dieting disordered subgroups were compared on levels of self-esteem. METHOD: One hundred and seventeen male and female patients diagnosed with anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified completed the Rosenberg Self-Esteem Scale (SES), the Coopersmith Self-Esteem Inventory (SEI), and measures of dieting disorder pathology and depression. RESULTS: No significant differences among the three dieting disorder subgroups were found. In determining convergent validity, regression analyses indicated that the SES was a significant predictor of dieting disorder psychopathology whereas the SEI was not. Of the two self-esteem measures, only the SES showed evidence of convergent validity. DISCUSSION: The results suggest that the SES has sounder construct and convergent validity than the SEI. Hence, the SES may be more appropriate for use with dieting disordered populations.

Perceptions of bed rest by anorexic patients.

OBJECTIVE: Few studies have investigated perceptions of operant conditioning programs by anorexic patients. This study examined patients' perceptions of the Bed Rest (BR) component which is employed in some operant conditioning programs. METHODS: A sample of 48 anorexic inpatients was administered a survey to elicit their attitudes towards BR. RESULTS: Results from the survey suggested that most patients perceived BR in a negative way. The main complaint, however, was not punishment or humiliation, as predicted, but isolation and boredom. A number of patients concluded that they wanted more individualization and distraction and less restriction while on BR. DISCUSSION: The findings justify the use of BR within a humane framework in the inpatient treatment of anorexia nervosa, but suggest that patients' perceptions of BR warrant systematic scrutiny.

Attentional biases in eating disorders: a visual probe detection procedure.

OBJECTIVE: To investigate attentional biases for body shape and weight-related stimulus words among subjects with anorexia nervosa, bulimia nervosa, and control subjects classified using a measure of dietary restraint. METHODS: A visual probe detection task was used to assess attention toward stimulus words reflecting either a thin or a large physique and positively or negatively valenced emotion words. RESULTS: In comparison to controls, subjects with eating disorders detected target probes more slowly when they appeared in the same location as had stimulus words connoting a thin physique. In addition, there was a trend toward faster detection or target probes that appeared in the same location as had stimulus words connoting a large physique. Neither of these effects were observed among restrained eaters. DISCUSSION: Our results extend prior work suggesting information-processing biases for body shape and weight-related stimuli among persons with eating disorders.

Conscious and preconscious processing of food, body weight and shape, and emotion-related words in women with anorexia nervosa.

OBJECTIVE: The present study was conducted to extend prior research on attention toward food and body weight and shape-related stimuli in women with eating disorders. METHOD: A modified Stroop color-naming task was completed by women with anorexia nervosa and by control females subdivided on a measure of dietary restraint. Eating disorder-relevant word categories included words connoting fatness, words connoting thinness, low caloric density food words, high caloric density food words, and neutral, control words. Valence effects were controlled for by including positively and negatively valenced emotion words. Stimuli were presented under both unmasked and masked conditions. RESULTS: Using unmasked stimuli, patients with anorexia nervosa, but not unrestrained or restrained eaters, had delayed color-naming latencies for both thin and fat word categories and, to a lesser extent, for high caloric density food words. No differences were observed with masked stimuli. DISCUSSION: Our findings suggest that both thinness and fatness are especially salient to women with anorexia. The lack of effects for emotion words suggests that these findings do not reflect a valence effect. We found no evidence for preconscious attentional biases in the masked condition.

Alcohol abuse and traumatic brain injury: effect on event-related potentials.

OBJECTIVE: To examine the individual and combined impact that traumatic brain injury (TBI) and heavy social use of alcohol have on electrophysiologic correlates of working memory and evaluation of task-relevant information. DESIGN: Case-control study. SETTING: University hospital brain injury rehabilitation unit. PARTICIPANTS: Forty male volunteers divided into four groups on the basis of their history of TBI and alcohol intake. Subjects with TBI had experienced a severe closed head injury at least 1 year before testing. MAIN OUTCOME MEASURE: Event-related potentials (ERPs) and neuropsychometric tests. RESULTS: Groups showed no significant differences in average age or neuropsychological tests. TBI groups did not differ in time postinjury or on severity measures. Alcohol use measures were significantly greater in the two alcohol groups. N200 latency and P300 amplitude were impaired in heavy social drinkers and in nondrinking subjects with TBI relative to controls, but were significantly impaired in subjects with TBI who were also heavy social drinkers. CONCLUSION: The results indicate that although alcohol use and TBI independently produce mile alterations in some aspects of late ERP components, the ERP changes are significantly greater when alcohol use and TBI are combined. This study provides evidence that heavy social drinking after TBI has a measurable impact on electrophysiologic correlates of cognition.

The role of autonomic arousal in problem gambling.

The present study investigated the role of arousal in problem gambling. Three groups of subjects were recruited into the study corresponding to problem gamblers, high and low frequency social gamblers. For the two gambling groups, the preferred form of gambling was poker machine playing. Five different conditions were employed in order to determine under which conditions gambling related cues were related to increased autonomic arousal, as measured by skin conductance level (SCL), heart rate (HR) and frontalis electromyography (EMG). The five conditions were a neutral task, a videotaped poker machine gambling scenario presented with and without distraction, a personally relevant "win" situation and a videotaped horse race. Comparisons between responses for the videotaped poker machine gambling stimuli versus a horse-racing video task demonstrated differences only for the problem gambling group and only for SCL. No differences between these tasks emerged on the HR and EMG indices and no differences were evident for either of the social gambling groups. No changes were observed in any group when subject's cognitions were prevented by asking patients to count the number of wins made during the video play period while watching the same poker machine video. However, when personally relevant situations were presented and compared to a neutral task, differences were observed in all three groups. However, the nature of these differences varied between the groups and the different indices of arousal. For problem gamblers, increases were evident in all three measures. Increases were also observed for the control groups in comparison to the neutral task, but only in HR and SCL and not for EMG. For HR, the increases were equivalent across all three gambling groups. However, for SCL the problem gambling group became significantly more aroused than the control groups, but no differences were observed between the high and low frequency gamblers. Only the problem gambling groups evidenced significant increases in the personally relevant task compared to the neutral task for EMG. Theoretical and clinical implications of these results for the development, maintenance and treatment of problematic levels of gambling are discussed.

Cognitive-behavioural therapy versus EMG biofeedback in the treatment of chronic low back pain.

Forty-four chronic, but relatively well functioning, low back pain patients were assigned to either Cognitive Behaviour Therapy (CBT). Electromyographic Biofeedback (EMGBF) or Wait List Control (WLC). Both treatments were conducted over eight sessions in groups of four subjects. Results at post-treatment indicated significant improvements in functioning on measures of pain intensity, perceived level of disability, adaptive beliefs about pain and the level of depression in both the CBT and EMGBF conditions. These improvements were not evident for the WLC condition. At 6 months follow-up, treatment gains were maintained in the areas of pain intensity, pain beliefs, and depression, for both treatment groups, with further improvements occurring in anxiety and use of active coping skills. No significant differences were found between CBT and EMGBF on any of the outcome measures at either post-treatment or at 6 months follow-up. Further research is required to determine the degree to which these results reflect the mild level of psychological impairment and disability status of patients in the present study.

Family planning needs of male chronic mental patients in the general hospital psychiatry clinic.

We investigated the parenting history, contraceptive behavior, and contraceptive needs of 35 male chronic mental patients seen at an urban outpatient psychiatric clinic. Most patients had fathered children, but 60% of the children less than 16 years of age were not being reared by their biological father. Forty-one percent of the patients who had sexual intercourse during the preceding year and had not wanted children reported that they or their sexual partner had not used contraception at the time of last intercourse. Patients were reportedly at significant risk of fathering unwanted children and sexually transmitted diseases. Strategies for preventing unwanted pregnancies within this population are discussed.

PIP: Female chronic mental patients are likely to have induced abortions, give up children for others to raise, and to engage in unprotected sexual intercourse. There are few studies, however, on the family planning attitudes and needs of male psychiatric patients. 35 male chronic mental patients aged 23-49 years of mean age 36 at the psychiatric outpatient clinic of a publicly-funded general hospital in the Harris County district of Houston, Texas, responded to interview questions about their social situation, medical and sexual histories, previous children, attitudes toward family planning and contraceptive practices, and sources of information about family planning. Findings on their knowledge of AIDS and health locus of control are reported under separate cover. The hospital serves predominantly indigent and uninsured patients. Men 50 years or older were excluded from consideration in the study because it was thought they would be less likely to father future children. The sample was comprised of 30 black males, 4 white males, and one Hispanic male of mean education 11 years. Five men were currently married and nine more had been married at some point in the past. Patients had been attending the clinic for an average of 7 years, in a range of 0.5-27 years, with 17% reporting histories of psychiatric hospitalization within the past year. Diagnoses taken from patients' charts included schizophrenia among 26, schizoaffective disorder among two, organic mental disorder among four, and major affective disorder among two; one patient had an Axis II diagnosis of a severe personality disorder. All patients were being treated with psychotropic medications and all but three were being treated with neuroleptics. The interviews took place over the course of 9 months. 18 patients reported having fathered a total of 41 children. 60% of the children less than 16 years old, however, were not being raised by their biological father. 57% of the men reported having had sexual intercourse within the last year, with 26% reporting three or more sex partners during the period. 41% of the men who had sexual intercourse during the preceding year and had not wanted children reported that they or their sex partner had not used contraception during the most recent episode of intercourse. Many patients in the sample were therefore at significant risk of fathering unwanted children and contracting and/or transmitting sexually transmitted diseases. The authors discuss strategies for preventing unwanted pregnancies within this population.

A standard measure for exercise prescription for aqua running.

Aqua running has been promoted as a method for cardiovascular conditioning for the injured athlete as well as for others who desire a low impact aerobic workout. Recent studies have suggested the need for an environment-specific measure of exercise intensity. Twenty healthy subjects, 10 men and 10 women, underwent a graded exercise test of aqua running to investigate the relationship between cadence and heart rate. This was done to determine the utility of cadence as a measure for exercise prescription. The graded exercise test followed a standard protocol for exercise testing in aqua running. Results demonstrated a high correlation between cadence and heart rate, both as a group as well as individually. We conclude that cadence may be used as a measure for exercise prescription for aqua running.