Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer

The phosphatidylinositol 3-kinase (PI3K) pathway is a critical signal transduction pathway that regulates multiple cellular functions. Aberrant activation of this pathway has been identified in a wide range of cancers. Several pathway components including AKT, PI3K and mTOR represent potential therapeutic targets and many small molecule inhibitors are in development or early clinical trials. The complex regulation of the pathway, together with the multiple mechanisms by which it can be activated, make this a highly challenging pathway to target. For successful inhibition, detailed molecular information on individual tumours will be required and it is already clear that different tumour types show distinct combinations of alterations. Recent results have identified alterations in pathway components PIK3CA, PTEN, AKT1 and TSC1 in bladder cancer, some of which are significantly related to tumour phenotype and clinical behaviour. Co-existence of alterations to several PI3K pathway genes in some bladder tumours indicates that these proteins may have functions that are not related solely to the known canonical pathway

The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates.

OBJECTIVES: Many studies have examined the prevalence and predictive validity of axis II personality disorders among unipolar depressed patients, but few have examined these issues among bipolar patients. The few studies that do exist suggest that axis II pathology complicates the diagnosis and course of bipolar disorder. This study examined the prevalence of axis II disorder in bipolar patients who were clinically remitted. METHODS: We assessed the co-occurrence of personality disorder among 52 remitted DSM-III-R bipolar patients using a structured diagnostic interview, the Personality Disorder Examination (PDE). RESULTS: Axis II disorders can be rated reliably among bipolar patients who are in remission. Co-diagnosis of personality disorder occurred in 28.8% of patients. Cluster B (dramatic, emotionally erratic) and cluster C (fearful, avoidant) personality disorders were more common than cluster A (odd, eccentric) disorders. Bipolar patients with personality disorders differed from bipolar patients without personality disorders in the severity of their residual mood symptoms, even during remission. CONCLUSIONS: When structured assessment of personality disorder is performed during a clinical remission, less than one in three bipolar patients meets full syndromal criteria for an axis II disorder. Examining rates of comorbid personality disorder in broad-based community samples of bipolar spectrum patients would further clarify the linkage between these sets of disorders

A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder.

BACKGROUND: Bipolar patients are at risk for relapses of their illness even when undergoing optimal pharmacotherapy. This study was performed to determine whether combining family-focused therapy (FFT) with pharmacotherapy during a postepisode interval enhances patients' mood stability during maintenance treatment. METHODS: In a randomized controlled trial, 101 bipolar patients were assigned to FFT and pharmacotherapy or a less intensive crisis management (CM) intervention and pharmacotherapy. Outcome assessments were conducted every 3 to 6 months for 2 years. Participants (mean +/- SD age, 35.6 +/- 10.2 years) were referred from inpatient or outpatient clinics after onset of a manic, mixed, or depressed episode. FFT consisted of 21 sessions of psychoeducation, communication training, and problem-solving skills training. Crisis management consisted of 2 sessions of family education plus crisis intervention sessions as needed. Both protocols lasted 9 months. Patients received pharmacotherapy for 2 study years. Main outcome measures included time to relapse, depressive and manic symptoms, and medication adherence. RESULTS: Rates of study completion did not differ across the FFT (22/31, 71%) and CM groups (43/70, 61%). Patients undergoing FFT had fewer relapses (11/31, 35%) and longer survival intervals (mean +/- SD, 73.5 +/- 28.8 weeks) than patients undergoing CM (38/70, 54%; mean +/- SD, 53.2 +/- 39.6 weeks; hazard ratio, 0.38; 95% confidence interval, 0.20-0.75; P =.003; intent to treat). Patients undergoing FFT showed greater reductions in mood disorder symptoms and better medication adherence during the 2 years than patients undergoing CM. CONCLUSION: Combining family psychoeducation with pharmacotherapy enhances the postepisode symptomatic adjustment and drug adherence of bipolar patients

Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy.

BACKGROUND: Few studies have examined the combined effects of psychosocial treatment and pharmacotherapy for bipolar disorder. This study used a randomized, controlled design to examine a 9-month, manual-based program of family-focused psychoeducational treatment (FFT). METHODS: Bipolar patients (N = 101) were recruited shortly after an illness episode and randomly assigned to 21 sessions of FFT (n = 31) or to a comparison treatment involving two family education sessions and follow-up crisis management (CM; n = 70). Both treatments were delivered over 9 months; patients were simultaneously maintained on mood stabilizing medications. Patients were evaluated every 3 months for 1 year as to relapse status, symptom severity, and medication compliance. RESULTS: Patients assigned to FFT had fewer relapses and longer delays before relapses during the study year than did patients in CM. Patients in FFT also showed greater improvements in depressive (but not manic) symptoms. The most dramatic improvements were among FFT patients whose families were high in expressed emotion. The efficacy of FFT could not be explained by differences among patients in medication regimes or compliance. CONCLUSIONS: Family-focused psychoeducational treatment appears to be an efficacious adjunct to pharmacotherapy for bipolar disorder. Future studies should evaluate family treatment against other forms of psychotherapy matched in amount of therapist-patient contact

Involving relatives in relapse prevention for bipolar disorder: a multi-perspective qualitative study of value and barriers

Background Managing early warning signs is an effective approach to preventing relapse in bipolar disorder. Involving relatives in relapse prevention has been shown to maximize the effectiveness of this approach. However, family-focused intervention research has typically used expert therapists, who are rarely available within routine clinical services. It remains unknown what issues exist when involving relatives in relapse prevention planning delivered by community mental health case managers. This study explored the value and barriers of involving relatives in relapse prevention from the perspectives of service users, relatives and care-coordinators. Methods Qualitative interview study nested within a randomized controlled trial of relapse prevention for individuals with bipolar disorder. The purposive sample of 52 participants comprised service users (n = 21), care coordinators (n = 21) and relatives (n = 10). Data were analyzed using a grounded theory approach. Results All parties identified benefits of involving relatives in relapse prevention: improved understanding of bipolar disorder; relatives gaining a role in illness management; and improved relationships between each party. Nevertheless, relatives were often discouraged from becoming involved. Some staff perceived involving relatives increased the complexity of their own role and workload, and some service users valued the exclusivity of their relationship with their care-coordinator and prioritized taking individual responsibility for their illness over the benefits of involving their relatives. Barriers were heightened when family relationships were poor. Conclusions Whilst involving relatives in relapse prevention has perceived value, it can increase the complexity of managing bipolar disorder for each party. In order to fully realize the benefits of involving relatives in relapse prevention, additional training and support for community care coordinators is needed. Trial registration ISRCTN4135263

Estabilidade no prognóstico do perfil de aptidão física de jovens atletas de handebol

Este estudo teve como objetivo: 1) verificar a estabilidade do perfil de aptidão física de jovens atletas de handebol durante a adolescência; e 2) comparar os resultados com a seleção paulista adulta feminina. Para tanto, a amostra foi constituída por cinco jovens atletas de handebol feminino que foram seguidas semilongitudinalmente por dois anos, com média de idade e tempo de prática inicial e final de 14,2 ± 1,3 anos, 18,4 ± 10,7 meses e 16,2 ± 1,3 anos, 42,8 ± 10,7 meses, respectivamente (12h/semana de treinamento). Na temporada de 1997 quatro atletas foram pré-selecionadas para a seleção brasileira de cadetes. As variáveis mensuradas foram: peso corporal (P); altura total (A); impulsão vertical sem (IVS) e com auxílio dos membros superiores (IVC); impulsão horizontal (IH); agilidade (SR); velocidade (50m) e potência anaeróbica (40seg.), seguindo padronização CELAFISCS. Os coeficientes de Pearson e Spearman foram significativamente altos e muitos altos (p < 0,05) para P (0,88), A (0,98 e 0,99), 50m (0,95 e 0,90) e 40seg. (0,87 e 0,90). Estes dados permitem concluir que as jovens atletas apresentaram alta estabilidade nas variáveis antropométricas, velocidade e potência anaeróbica durante um período de dois anos da adolescência, favorecendo a hipótese de que a expectativa de sucesso esportivo pode ser predita em idades precoces