Three new BLM gene mutations associated with Bloom syndrome.

Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information.

Medical and substance-related comorbidity in bipolar disorder: translational research and treatment opportunities.

It is well established that individuals with bipolar disorder are differentially affected by substance-related as well as medical disorders (ie, cardiometabolic disorders, respiratory disorders, neurological disorders, and infectious diseases). Emerging evidence indicates that some comorbid conditions (eg, diabetes mellitus) in bipolar individuals may be subserved by overlapping neurobiological networks. Disturbances in glucocorticoid/insulin signaling and immunoinflammatory effector systems are points of pathophysiological commonality between bipolar disorder and "stress-sensitive" medical disorders. Subphenotyping bipolar disorder as a function of comorbidity and temporality of onset may provide an opportunity for refining disease pathophysiological models and developing innovative disease-modifying therapies.

Assessment of suicidal behavior and factors associated with a diagnosis of prostate cancer.

OBJECTIVES: To determine the incidence of suicide risk in a group of patients who have been diagnosed with localized prostate cancer (PC) and to identify the factors that affect suicidal behavior. METHODS: Patients from a tertiary care oncology center in São Paulo, Brazil participated in this study and were interviewed after being diagnosed with low-risk or intermediate-risk PC, per the D'Amico risk classification, between September 2015 and March 2016. Patients underwent suicide risk assessment sessions using the Mini International Neuropsychiatric Interview (MINI), the Hospital Anxiety and Depression Scale (HADS), and the CAGE substance abuse screening tool before they started treatment and surveillance. Psychiatric treatment history, family history of suicidal behavior, and the use of psychotropic drugs were also examined. RESULTS: The prevalence of suicide risk among 250 patients who were recently diagnosed with low-risk or intermediate-risk PC was 4.8%. According to the HADS, 10.8% and 6.8% of patients had a positive score anxiety and for depression, respectively. Alcoholism was suspected in 2.8% of the group. Suicide risk was associated with anxiety (p=0.001); depression (p=0.005); being divorced, separated, widowed, or single (p=0.045); living alone (p=0.028); and prior psychological treatment (p=0.003). CONCLUSIONS: After being diagnosed with PC, patients who display risk factors for suicide should be monitored by a mental health team.

Metastatic breast cancer: do current treatments improve quality of life? A prospective study.

CONTEXT AND OBJECTIVE: In metastatic breast cancer cases, the currently available therapeutic approaches provide minimal improvement in survival. As such, quality of life (QOL) becomes one of the main objectives of treatment. It is not known whether current treatments derived from trials improve QOL. The aim was to evaluate changes in QOL among metastatic breast cancer patients receiving treatment derived from trials. DESIGN AND SETTING: Prospective observational QOL survey in a tertiary cancer center. METHODS: To evaluate the influence of current treatments on patients' QOL, the Medical Outcomes Study Short Form-36 (SF-36) and the Beck Depression Inventory (BDI) were applied on three occasions: before starting treatment and at the 6th and 12th weeks, to consecutive metastatic breast cancer patients over a one-year period. RESULTS: We found an improvement in QOL in the sample evaluated (n = 40), expressed by changes in the overall SF-36 score (p = 0.002) and the BDI (p = 0.004). Taken individually, the SF-36 components Pain, Social Functioning and Mental Health also improved significantly. Patients with worse initial performance status and secondary symptoms displayed greater improvement than those with better initial performance status and asymptomatic disease (p < 0.001). Patients who received more than one type of therapy showed larger gains than those given only one type (p = 0.038). CONCLUSIONS: In our environment, current metastatic breast cancer treatments can improve QOL, especially among symptomatic patients and those with low performance status.

The level of nicotine dependence is an independent risk factor for cancer: a case control study.

BACKGROUND: Less than 20% of lifetime smokers will ever develop cancer. Smoking habits characteristics, particularly the level of nicotine dependence level, were not fully evaluated as a marker of risk. METHODS: Case-control study of voluntary patients prospectively enrolled in a smoking cessation program in a cancer hospital. For each cancer case, patients of the same age and sex were selected. The Beck Depression Inventory, an instrument for the diagnosis of depressive mood and clinical depression, and the Fagerström Test Questionnaire, a questionnaire that has a good correlation with nicotine levels, used to determine the degree of dependence on nicotine, were applied. Age on admission to the study, sex, and number of pack-years were also evaluated. RESULTS: From May 1999 to May 2002, 56 cancer patients (case) and 85 matching controls (control) were identified in the population studied. There was no difference regarding pack-years. Fagerström Test Questionnaire was significantly higher in patients with cancer (7.5+/-1.9) compared to controls (6.3+/-2.0). We found a Fagerström Test Questionnaire>7 in 73.2% of the cancer cases versus 43.5% of the controls (p=0.001). The proportion of depressed patients was higher in the cancer group (37.5% x 17.6%). Logistic regression adjusted for age and tobacco consumption disclosed that Fagerström Test Questionnaire score>7 has an odds ratio for cancer of 3.45 (95% CI 1.52-7.83, p=0.003). CONCLUSION: Fagerström Test Questionnaire higher than 7 was identified as a risk factor for cancer in smokers with similar tobacco consumption.

Stopping smoking: a prospective, randomized, double-blind study comparing nortriptyline to placebo.

OBJECTIVE: The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation. This study evaluates the efficacy of nortriptyline in an antismoking program. METHODS: A possible randomized double-blind study that included 144 patients who were randomized to receive nortriptyline, 75 mg/d (68 patients), or placebo (76 patients), during 6 consecutive weeks. All patients attended behavioral group orientation for 5 weeks. The rate of success, complications, adherence to the regime, and factors of pretreatment prognosis were evaluated (multivariate analysis). RESULTS: The groups were balanced in relation to the characteristics of the patients on entering the study. Patients receiving nortriptyline showed significantly higher cessation rate (55.9%) compared to the group receiving placebo (23.3%; p < 0.001). In a univariate analysis on prognosis factors influencing the rate of cessation in our study, the Fagerström test results (p = 0.005) and nortriptyline (p < 0.001) were identified. Logistic regression showed that a Fagerström test score of < 7 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.47 to 6.7; p = 0.003) and nortriptyline use (OR, 4.1; 95% CI, 2 to 8.3; p < 0.001) were independent factors impacting the rate of success for smoking cessation. No significant complications were observed in the nortriptyline group. CONCLUSION: This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers, as compared to the placebo group, without any significant side effects.

Clinical and demographic profile of cancer patients in a consultation-liaison psychiatric service.

CONTEXT: An almost 50% prevalence of psychiatric disorders among cancer patients has prompted a series of studies on consultation-liaison psychiatry. Nonetheless, there are few reports on the epidemiological factors involving comorbidity between cancer and psychiatric disorders. OBJECTIVE: To evaluate the epidemiological profile of cancer inpatients referred to the consultation-liaison psychiatric service in an oncology hospital during its first year of activity. TYPE OF STUDY: Descriptive study. SETTING: Tertiary-care teaching hospital. PARTICIPANTS: 319 patients referred 412 times to the consultation-liaison psychiatry service. PROCEDURES: From August 97 to July 98, an appraisal was made of data on all admissions registered at the Hospital do C ncer, and also all referrals registered at the consultation-liaison psychiatry service. MAIN MEASUREMENTS: The demographics and patients' clinical data, the type and flow of the request, and the evaluation conducted by the service were analyzed and comparisons with the hospital data were made. The distribution of the number of referrals was used to construct a profile of patients who had repeatedly used the service. RESULTS: Psychiatric diagnoses were found in 59% of the cases. Forty-three percent of these required medication, 18.3% needed psychotherapy, 22.1% family intervention and 20.5% guidance from the staff. Over 22.8% of the consultations were reevaluations, mainly involving younger male patients with worst prognoses. These patients required lengthier and more elaborate intervention, and had higher prevalence of depressive and behavioral disorders. CONCLUSION: A younger and mainly male population of non-surgical oncological cases was referred to the consultation-liaison psychiatric service during its first year of activity. The psychiatric disorder prevalence was higher than expected, and consisted predominantly of mood disorders. We detected a priority group, namely the reevaluated patients, who deserved special attention throughout the psychiatric interventions.

Assessment of suicidal behavior and factors associated with a diagnosis of prostate cancer

OBJECTIVES: To determine the incidence of suicide risk in a group of patients who have been diagnosed with localized prostate cancer (PC) and to identify the factors that affect suicidal behavior. METHODS: Patients from a tertiary care oncology center in São Paulo, Brazil participated in this study and were interviewed after being diagnosed with low-risk or intermediate-risk PC, per the D'Amico risk classification, between September 2015 and March 2016. Patients underwent suicide risk assessment sessions using the Mini International Neuropsychiatric Interview (MINI), the Hospital Anxiety and Depression Scale (HADS), and the CAGE substance abuse screening tool before they started treatment and surveillance. Psychiatric treatment history, family history of suicidal behavior, and the use of psychotropic drugs were also examined. RESULTS: The prevalence of suicide risk among 250 patients who were recently diagnosed with low-risk or intermediate-risk PC was 4.8%. According to the HADS, 10.8% and 6.8% of patients had a positive score anxiety and for depression, respectively. Alcoholism was suspected in 2.8% of the group. Suicide risk was associated with anxiety (p=0.001); depression (p=0.005); being divorced, separated, widowed, or single (p=0.045); living alone (p=0.028); and prior psychological treatment (p=0.003). CONCLUSIONS: After being diagnosed with PC, patients who display risk factors for suicide should be monitored by a mental health team.

The association between conventional antidepressants and the metabolic syndrome: a review of the evidence and clinical implications.

Major depressive disorder is a prevalent recurrent medical syndrome associated with inter-episodic dysfunction. The metabolic syndrome is comprised of several established risk factors for cardiovascular disease (i.e. abdominal obesity, dyslipidaemia, dysglycaemia and hypertension). The criterion items of the metabolic syndrome collectively represent a multi-dimensional risk factor for cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates that both major depressive disorder and the metabolic syndrome, albeit distinct, often co-occur and are possibly subserved by overlapping pathophysiology and causative mechanisms. Conventional antidepressants exert variable effects on constituent elements of the metabolic syndrome, inviting the need for careful consideration prior to treatment selection and sequencing. Initiating and maintaining antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.

Desvenlafaxine in the treatment of major depressive disorder.

Major depressive disorder (MDD) is among the most incapacitating conditions in the world. The emergence of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) antidepressants has improved the treatment of MDD. Desvenlafaxine succinate (DVS) is the succinate salt of the isolated major active metabolite of venlafaxine, O-desmethylvenlafaxine: it is the third SNRI to become available in the United States, and was approved in 2008 by the US Food and Drug Administration (FDA) for the treatment of MDD. Early investigations showed therapeutic efficacy for doses between 50 and 400 mg/day; however in doses above 100 mg/day there were incremental increases in side effects. Nausea was the most frequent adverse effect. Hence the recommended dosing for DVS is in the 50 to 100 mg range. Desvenlafaxine is excreted in urine, it is minimally metabolized via the CYP450 pathway, and is a weak inhibitor of CYP2D6. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other SNRI. Further head-to-head trials involving comparisons of DVS in the 50 to 100 mg dose range with currently available SSRI and SNRI antidepressants are required. Evidence for relapse prevention is available in the 200 to 400 mg dose range, but this needs to be demonstrated in the 50 to 100 mg dose range, as well as health economic measures and quality of life evaluations.

Quetiapine XR efficacy and tolerability as monotherapy and as adjunctive treatment to conventional antidepressants in the acute and maintenance treatment of major depressive disorder: a review of registration trials.

Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 - 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.

Mutations in the MECP2 gene are not a major cause of Rett syndrome-like or related neurodevelopmental phenotype in male patients.

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.

Metastatic breast cancer: do current treatments improve quality of life? A prospective study / Câncer de mama metastático: a abordagem atual melhora a qualidade de vida? Um estudo prospectivo

CONTEXT AND OBJECTIVE: In metastatic breast cancer cases, the currently available therapeutic approaches provide minimal improvement in survival. As such, quality of life (QOL) becomes one of the main objectives of treatment. It is not known whether current treatments derived from trials improve QOL. The aim was to evaluate changes in QOL among metastatic breast cancer patients receiving treatment derived from trials. DESIGN AND SETTING: Prospective observational QOL survey in a tertiary cancer center. METHODS: To evaluate the influence of current treatments on patients' QOL, the Medical Outcomes Study Short Form-36 (SF-36) and the Beck Depression Inventory (BDI) were applied on three occasions: before starting treatment and at the 6th and 12th weeks, to consecutive metastatic breast cancer patients over a one-year period. RESULTS: We found an improvement in QOL in the sample evaluated (n = 40), expressed by changes in the overall SF-36 score (p = 0.002) and the BDI (p = 0.004). Taken individually, the SF-36 components Pain, Social Functioning and Mental Health also improved significantly. Patients with worse initial performance status and secondary symptoms displayed greater improvement than those with better initial performance status and asymptomatic disease (p < 0.001). Patients who received more than one type of therapy showed larger gains than those given only one type (p = 0.038). CONCLUSIONS: In our environment, current metastatic breast cancer treatments can improve QOL, especially among symptomatic patients and those with low performance status.

CONTEXTO E OBJETIVO: As abordagens terapêuticas atuais para o câncer de mama metastático não asseguram aumento na sobrevida. Sendo assim, qualidade de vida passa a ser um dos principais objetivos do tratamento. Apesar disso, desconhecemos a influência dos tratamentos atualmente utilizados na qualidade de vida dessa população. O objetivo do estudo foi avaliar a influência do tratamento oncológico na qualidade de vida de portadoras de câncer de mama metastático. TIPO DE ESTUDO E LOCAL: Estudo prospectivo da variação da qualidade de vida de portadoras de câncer de mama metastático tratadas em um centro médico terciário. MÉTODOS: Realizamos um levantamento prospectivo da influência dos tratamentos oncológicos, incluindo quimioterapia, tratamento hormonal, radioterapia, cirurgia e suporte clínico, na qualidade de vida de pacientes tratadas no Centro de Tratamento e Pesquisa Hospital do Câncer, em São Paulo. Utilizamos para isso o Medical Outcomes Study's Short Form-36 (SF-36) e o Inventário de Depressão de Beck (IDB), aplicados em três ocasiões: antes do início, na 6ª e na 12ª semanas após o início do tratamento. RESULTADOS: Encontramos melhora de qualidade de vida na amostra avaliada (n = 40), expressa pela variação dos índices do SF-36 (p = 0,002) e do IDB (p = 0,004). Os componentes do SF-36 que apresentaram ganhos mais significativos foram dor, aspecto social e saúde mental. Como esperado, as pacientes com piores Performance Status (PS) e com sintomas secundários presentes apresentaram maiores ganhos em sua qualidade de vida que as de bom PS e as assintomáticas (p < 0,001). Da mesma forma, aquelas que receberam mais de uma modalidade terapêutica em comparação com as que só receberam um tipo de tratamento (p = 0,038). CONCLUSÕES: Em nosso meio, a abordagem atual para o câncer de mama metastático mostrou-se capaz de melhorar a qualidade de vida das pacientes, especialmente das que se apresentam com sintomas secundários à doença de base ou com baixo PS.

The level of nicotine dependence is an independent risk factor for cancer: a case control study

OBJETIVO: Menos de 20% dos fumantes crônicos desenvolverá cancer. As características do hábito de fumar, particularmente o nível de dependência à nicotina, não foram avaliadas inteiramente como um marcador do risco. MÉTODOS: Estudo caso-controle de pacientes voluntários, registrados prospectivamente em um programa de cessação de tabagismo em um hospital de cancer. Para cada caso de cancer, pacientes da mesma idade e sexo foram selecionados. O inventário de depressão de Beck, um instrumento validado para diagnóstico de estado depressivo e depressão clínica e o questionário de tolerância de Fagerstron , que é usado para determinar o grau de dependência e tem boa correlação com níveis de nicotina, foram aplicados. Idade na admissão ao estudo, sexo, número de maços-anos fumados foram avaliados também. RESULTADOS: De maio de 1999 a maio de 2002, 56 pacientes de câncer (caso) e 85 controles pareados (controle) foram identificados na população estudada . Não houve diferença quanto ao número de maços-ano. O questionário de tolerância de Fagerstron foi significativamente mais elevado nos pacientes com câncer (7.5 ± 1.9) comparado aos controles (6.3 ± 2.0). Encontramos um questionário de tolerância de Fagerstron > 7 em 73.2% dos casos de câncer, contra 43.5% dos controles (p=0.001). A proporção de pacientes deprimidos foi mais elevada no grupo do cancer (37.5% x 17.6%). A regressão logística, ajustada para a idade e o consumo do tabaco, apontou que uma contagem de questionário de tolerância de Fagerstron > 7 tem uma razão de chance para câncer de 3.45 (CI 95% 1.52 - 7.83, p = 0.003). CONCLUSAO: Resultado no questionário de tolerância de Fagerstron maior que 7 foi identificado como um fator de risco para cancer em fumantes com consumo similar do tabaco.

Clinical and demographic profile of cancer patients in a consultation-liaison psychiatric service

ABSTRACT CONTEXT: An almost 50 percent prevalence of psychiatric disorders among cancer patients has prompted a series of studies on consultation-liaison psychiatry. Nonetheless, there are few reports on the epidemiological factors involving comorbidity between cancer and psychiatric disorders. OBJECTIVE: To evaluate the epidemiological profile of cancer inpatients referred to the consultation-liaison psychiatric service in an oncology hospital during its first year of activity. TYPE OF STUDY: Descriptive study. SETTING: Tertiary-care teaching hospital. PARTICIPANTS: 319 patients referred 412 times to the consultation-liaison psychiatry service. PROCEDURES: From August 97 to July 98, an appraisal was made of data on all admissions registered at the Hospital do Câncer, and also all referrals registered at the consultation-liaison psychiatry service. MAIN MEASUREMENTS: The demographics and patients' clinical data, the type and flow of the request, and the evaluation conducted by the service were analyzed and comparisons with the hospital data were made. The distribution of the number of referrals was used to construct a profile of patients who had repeatedly used the service. RESULTS: Psychiatric diagnoses were found in 59 percent of the cases. Forty-three percent of these required medication, 18.3 percent needed psychotherapy, 22.1 percent family intervention and 20.5 percent guidance from the staff. Over 22.8 percent of the consultations were reevaluations, mainly involving younger male patients with worst prognoses. These patients required lengthier and more elaborate intervention, and had higher prevalence of depressive and behavioral disorders. CONCLUSION: A younger and mainly male population of non-surgical oncological cases was referred to the consultation-liaison psychiatric service during its first year of activity. The psychiatric disorder prevalence was higher than expected, and consisted predominantly of mood disorders. We detected a priority group, namely the reevaluated patients, who deserved special attention throughout the psychiatric interventions

Consenso sobre o tratamento da dependência de nicotina / Consensus on the treatment of nicotine dependence

Têm sido atribuídas à dependência de nicotina 20 por cento das mortes nos EUA. Estudos têm mostrado que 30 por cento a 50 por cento das pessoas que começam a fumar escalam para um uso problemático. Nos últimos 20 anos, a educaçäo e a persuasäo näo foram suficientes para promover uma mudança política, cultural e social relacionada ao comportamento de fumar. As intervenções para interromper o uso de tabaco ainda näo estäo integradas às rotinas dos serviços de saúde no mundo. A falta de estratégias de integraçäo, de tempo disponível para acoplar ações assistenciais mais específicas e mesmo a percepçäo dos profissionais de saúde de que os tratamentos para dependência de nicotina säo pouco efetivos säo algumas das barreiras apontadas. Assim, elaborar um consenso sobre a dependência de nicotina teve como objetivos: - levantar dados epidemiológicos relevantes relacionados ao uso do tabaco no mundo e no Brasil; - revisar ações gerais e centrais da nicotina; - elaborar um protocolo de triagem mínimo para serviços de atençäo primária à saúde; - recomendar diretrizes básicas de avaliaçäo, diagnóstico e tratamento para todos os níveis de atençäo à saúde em relaçäo à dependência da nicotina; - fornecer sugestões para a abordagem de grupos especiais de pacientes: adolescentes, gestantes, idosos, pacientes em regime de internaçäo, obesos e pacientes com comorbidade psiquiátricas, cardiovasculares e respiratórias

Exame otorrinolaringológico, cinefluoroscopia e análise perceptual auditiva em crianças com indicaçäo de adenoidectomia / Otolaryngologic examination, cineradiography and hearing perceptual analysis in children with adenoidectomy indication

No presente trabalho foram avaliadas as relaçöes entre os exames otorrinolaringológico, cinefluoroscopia e análise perceptual auditiva, efetuados em 20 criançass com indicaçäo cirúrgica de remoçäo de adenóide. Entre os parâmetros observados concluímos que foi de grande importância a movimentaçäo das paredes laterais da faringe e o grau de obstruçäo da coluna área na relaçäo entre o tamanho da adenóide e o tamanho da rinofaringe. Por sua vez, os dados da análise perceptual auditiva foram correspondentes aos achados cinefluoroscópicos