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P Brambilla

Publications and source records attributed to P Brambilla.

At least 19 recordsLinked to original sources

Crossvalidation of anthropometry against magnetic resonance imaging for the assessment of visceral and subcutaneous adipose tissue in children.

BACKGROUND: The study of the relationship between anthropometry and visceral adipose tissue (VAT) is of great interest because VAT is associated with many risk factors for noncommunicable diseases and anthropometry is easy to perform in clinical practice. The studies hitherto available for children have, however, been performed on small sample sizes. DESIGN: Pooling of the data of studies published from 1992 to 2004 as indexed on Medline. AIMS: To assess the relationship between anthropometry and VAT and subcutaneous adipose tissue (SAT) as measured by magnetic resonance imaging (MRI) in children and to analyze the effect of age, gender, pubertal status and ethnicity. SUBJECTS AND METHODS: Eligible subjects were 7-16 year-old, with availability of VAT and SAT, gender, ethnicity, body mass index (BMI) and waist circumference (WC). A total of 497 subjects were collected from seven different investigators and 407 of them (178 Caucasians and 229 Hispanics) were analyzed. RESULTS: Despite ethnic differences in MRI data, BMI, WC and age, no difference in VAT was found between Caucasians and Hispanics after correction for SAT and BMI. Univariate regression analysis identified WC as the best single predictor of VAT (64.8% of variance) and BMI of SAT (88.9% of variance). The contribution of ethnicity and gender to the unexplained variance of the VAT-WC relationship was low (< or =3%) but significant (P < or =0.002). The different laboratories explained a low (< or =4.8%) but significant (P < 0.0001) portion of the unexplained variance of the VAT-WC and SAT-BMI relationships. Prediction equations for VAT (VAT (cm(2)) = 1.1 x WC (cm)-52.9) and SAT (SAT (cm(2)) = 23.2 x BMI (kg/m(2))-329) were developed on a randomly chosen half of the population and crossvalidated in the remaining half. The pure error of the estimate was 13 cm(2) for VAT and 57 cm(2) for SAT. CONCLUSIONS: WC can be considered a good predictor of VAT as well as BMI of SAT. The importance of ethnicity and gender on VAT estimation is not negligible.

Adipose Tissue↗

Fluoxetine versus other types of pharmacotherapy for depression.

BACKGROUND: Depression is common in primary care and it is associated with marked personal, social and economic morbidity, and creates significant demands on service providers in terms of workload. Treatment is predominantly pharmaceutical or psychological. Fluoxetine, the first of a group of antidepressant (AD) agents known as selective serotonin reuptake inhibitors (SSRIs), has been studied in many randomised controlled trials (RCTs) in comparison with tricyclic (TCA), heterocyclic and related ADs, and other SSRIs. These comparative studies provided contrasting findings. In addition, systematic reviews of RCTs have always considered the SSRIs as a group, and evidence applicable to this group of drugs might not be applicable to fluoxetine alone. The present systematic review assessed the efficacy and tolerability profile of fluoxetine in comparison with TCAs, SSRIs and newer agents. OBJECTIVES: To determine the efficacy of fluoxetine, compared with other ADs, in alleviating the acute symptoms of depression, and to review its acceptability. SEARCH STRATEGY: Relevant studies were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (1966-2004) and Embase (1974-2004). Non-English language articles were included. SELECTION CRITERIA: Only RCTs were included. For trials which have a crossover design only results from the first randomisation period were considered. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers using a standard form. Responders to treatment were calculated on an intention-to-treat basis: drop-outs were always included in this analysis. When data on drop-outs were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were analysed including patients with a final assessment or with the last observation carried forward. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study and who experienced adverse reactions out of the total number of randomised patients. The primary analyses used a fixed effects approach, and presented Peto Odds Ratio (PetoOR) and Standardised Mean Difference (SMD). MAIN RESULTS: On a dichotomous outcome fluoxetine was less effective than dothiepin (PetoOR: 2.09, 95% CI 1.08 to 4.05), sertraline (PetoOR: 1.40, 95% CI 1.11 to 1.76), mirtazapine (PetoOR: 1.64, 95% CI 1.01 to 2.65) and venlafaxine (Peto OR: 1.40, 95% CI 1.15 to 1.70). On a continuous outcome, fluoxetine was more effective than ABT-200 (Standardised Mean Difference (SMD) random effects: - 1.85, 95% CI - 2.25 to - 1.45) and milnacipran (SMD random effects: - 0.38, 95% CI - 0.71 to - 0.06); conversely, it was less effective than venlafaxine (SMD random effect: 0.11, 95% CI 0.00 to 0.23), however these figures were of borderline statistical significance. Fluoxetine was better tolerated than TCAs considered as a group (PetoOR: 0.78, 95% CI 0.68 to 0.89), and was better tolerated in comparison with individual ADs, in particular than amitriptyline (PetoOR: 0.64, 95% CI 0.47 to 0.85) and imipramine (PetoOR: 0.79, 95% CI 0.63 to 0.99), and among newer ADs than ABT-200 (PetoOR: 0.21, 95% CI 0.10 to 0.41), pramipexole (PetoOR: 0.20, 95% CI 0.08 to 0.47) and reboxetine (PetoOR: 0.61, 95% CI 0.40 to 0.94). AUTHORS' CONCLUSIONS: There are statistically significant differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain, and no definitive implications for clinical practice can be drawn. From a clinical point of view the analysis of antidepressants' safety profile (adverse effect and suicide risk) remains of crucial importance and more reliable data about these outcomes are needed. Waiting for more robust evidence, treatment decisions should be based on considerations of clinical history, drug toxicity, patient acceptability, and cost. We need for large, pragmatic trials, enrolling heterogeneous populations of patients with depression to generate clinically relevant information on the benefits and harms of competitive pharmacological options. A meta-analysis of individual patient data from the randomised trials is clearly necessary.

Antidepressive Agents↗

Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data.

BACKGROUND: In the last ten years, SSRIs have increasingly replaced TCAs as comparators of newer antidepressants (ADs), because of their better tolerability profile. In particular, fluoxetine has become a reference drug for the treatment of depression, but the occurrence of individual side effects in depressed subjects treated with fluoxetine and each comparator AD have not been systematically investigated. METHODS: This meta-analysis investigated the frequency of side effects induced by fluoxetine or alternative ADs and compared the occurrence of individual side effects in depressed subjects. All randomised clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients with major depression were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. Two reviewers independently extracted information. RESULTS: Significantly less percentage of patients treated with fluoxetine experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs; RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %, 15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in comparison with other SSRIs. Regard to individual side effects, activating (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more frequent in fluoxetine-treated patients, whereas cholinergic side effects were significantly less frequent. CONCLUSIONS: Fluoxetine compared to other ADs had more activating and gastrointestinal adverse effects, which often require additional pharmacotherapy or other managements strategies, leading to discontinuation and non-compliance and increasing the costs. This information is relevant to base on evidence the prescription of ADs in everyday clinical practice.

Antidepressive Agents, Tricyclic↗

Stress and hippocampal abnormalities in psychiatric disorders.

The hippocampus plays a main role in regulating stress response in humans, but is itself highly sensitive to neurotoxic effects of repeated stressful episodes. Hippocampal atrophy related to experimental stress has been reported in laboratory studies in animals. Several controlled brain imaging studies have also shown hippocampal abnormalities in psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and borderline personality disorder (BPD). This paper reviews the physiological role of the hippocampus in stress circuitry and the effects of stress on cognitive functions mediated by the hippocampus. We also review brain imaging studies investigating hippocampus in PTSD, MDD, and BPD. This literature suggests that individuals with PTSD, MDD, and BPD may suffer hippocampal atrophy as a result of stressors associated with these disorders. Prospective, longitudinal studies will be needed in high-risk offspring and first-episode subjects to explore the relationship between stress and hippocampal atrophy in these neuropsychiatric illnesses.

Animals↗

Corpus callosum signal intensity in patients with bipolar and unipolar disorder.

BACKGROUND: Anatomical abnormalities in the corpus callosum have been reported in magnetic resonance imaging (MRI) studies in patients with bipolar but not unipolar disorder. MRI signal intensity can be used as a putative index of corpus callosum myelination. OBJECTIVES: To measure MRI signal intensity in patients with bipolar and unipolar disorder to investigate abnormalities of corpus callosum myelination. METHODS: The study involved 29 DSM-IV bipolar patients (mean (SD) age, 35 (11) years; 16 male, 13 female), 23 DSM-IV unipolar patients (41 (10) years; 4 male, 19 female), and 36 healthy controls (37 (10) years; 23 male, 13 female). A 1.5T GE Signa magnet was employed, with a fast spin echo sequence. Corpus callosum signal intensity was obtained blindly using the semiautomated software NIH Image 1.62. RESULTS: Bipolar patients had lower corpus callosum signal intensity for all callosal subregions (genu, anterior and posterior body, isthmus, splenium) than healthy controls (ANCOVA, age and sex as covariates, p<0.05). No significant differences were found between unipolar and healthy subjects (ANCOVA, age and sex as covariates, p>0.05). CONCLUSIONS: The findings suggest abnormalities in corpus callosum white matter in bipolar but not unipolar patients, possibly because of altered myelination. Such abnormalities could lead to impaired interhemispheric communication in bipolar disorder. Longitudinal MRI studies involving first episode and early onset bipolar patients will be necessary for a better understanding of the potential role of abnormalities of corpus callosum myelination in the pathophysiology of bipolar disorder.

Adult↗

GABAergic dysfunction in mood disorders.

The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local circuits. The role of GABAergic dysfunction in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area.

Brain Chemistry↗

[Treatment of childhood obesity].

This article provides current guidelines on the treatment and prevention of childhood obesity. Since factors involved in obesity change with age, the therapeutic approach in pre-school children will be different from pupils and adolescents. The treatment will also be modulated on the basis of weight excess, weight gain velocity and complications. The main goal of the treatment should be to encourage the child and his family to have healthy lifestyle. Families who are not ready for change might benefit from counselling to improve motivation before starting treatment. A detailed alimentary and behavioural history is the start point of the treatment. The strategy of the intervention is to induce changes at three levels: 1) attitudes of parents; 2) physical activity; 3) energy intake. The treatment of the adolescents should take into account the pubertal changes and the psychological aspects of this peculiar period of life. Obesity is a chronic disease and its treatment needs long-life follow-up. The long-term results of the obesity treatment are often disappointing and we have to consider consistent prevention programs for better results.

Adolescent↗

Clozapine-treated subjects with treatment-resistant schizophrenia: a systematic review of experimental and observational studies.

Randomized clinical trials have limitations because they focus on small samples of highly selected patients. Observational studies, which follow large cohorts of typical patients receiving pharmacological treatments, should overcome some of these trial limitations and provide information that cannot be generated with clinical trials. The present study aimed to compare experimental and observational studies of clozapine-treated subjects with treatment-resistant schizophrenia. A systematic review of experimental and observational studies evaluating clozapine-treated subjects in treatment-resistant schizophrenia was carried out. We identified 50 studies that met the inclusion criteria. Less than one-third of clinical trials enrolled more than 50 patients compared to 44% of prospective and nearly 90% of retrospective studies. In addition, 78% of prospective and 89% of retrospective observational studies lasted more than 12 weeks, while the majority of trials lasted less than 8 weeks. Most clinical trials defined treatment-resistant schizophrenia according to Kane's criteria, while the majority of observational studies adopted implicit criteria. In comparison with clinical trials, observational studies provided a higher weighted mean rate of clozapine-responders and a lower weighted mean rate of clozapine-dropouts. This literature survey suggests that the role of observational studies in the evaluation of medicines should be reconsidered. A new generation of observational studies should be developed to provide evidence on patient outcome in typical settings and under real-world circumstances, and on variables which may affect outcome.

Antipsychotic Agents↗

MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals.

The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age+/-S.D.=34.4+/-9.8 years), 17 unipolar patients (mean age+/-S.D.=42.8+/-9.2 years), and 39 healthy control subjects (mean age+/-S.D.=36.6+/-9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.

Adult↗

Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy.

BACKGROUND: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking. METHODS: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test. RESULTS: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003). CONCLUSIONS: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.

Absorptiometry, Photon↗

Decreased pituitary volume in patients with bipolar disorder.

BACKGROUND: Neuroendocrinologic investigations in bipolar disorder have suggested abnormalities in pituitary function. However, few imaging studies have evaluated possible anatomical differences in this brain structure in mood disorder patients. Our aim was to examine potential abnormalities in pituitary volume in patients with bipolar and in a comparison group of patients with unipolar disorder. METHODS: We measured the volumes of the pituitary gland in 23 patients with bipolar disorder (mean +/- s.d. = 34.3 +/- 9.9 years) and 13 patients with unipolar disorder (41.2 +/- 9.6 years), and 34 healthy control subjects (36.6 +/- 9.6 years) using 1.5 mm thick T1-weighted coronal 1.5 T MRI images. All measurements were done blindly by a trained rater. RESULTS: Patients with bipolar disorder had significantly smaller pituitary volumes than healthy control subjects (mean volume +/- s.d. = 0.55 +/- 0.15 ml and 0.68 +/- 0.20 ml, respectively; ANCOVA, F = 8.66, p = 0.005), and than patients with unipolar disorder (0.70 +/- 0.12 ml, F = 5.98, p = 0.02). No differences were found between patients with unipolar disorder and healthy control subjects (F = 0.01, p = 0.91). CONCLUSIONS: To our knowledge, this is the first study that reports smaller pituitary volumes in bipolar disorder. Our findings suggest that detectable abnormalities in pituitary size are present in patients with bipolar disorder, which may reflect a dysfunctional HPA axis.

Adult↗

Anatomical MRI study of basal ganglia in bipolar disorder patients.

This study examined possible anatomical abnormalities in basal ganglia structures in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus pallidus total volume were measured with magnetic resonance imaging (MRI) in 22 DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10 years). No significant differences were found between bipolar patients and healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05). Age was inversely correlated with left putamen volumes in patients (R=-0.44, P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients (>36 years old) had a significantly larger left globus pallidus than younger ones (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after entering age as independent variable, the length of illness predicted smaller left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03). No significant effects of episode type, number of prior episodes, or gender were found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our findings indicate that the basal ganglia may be anatomically preserved in bipolar patients. This is in contrast to available findings for unipolar disorder. However, our findings also suggest that age and length of illness may have significant effects on basal ganglia structures in bipolar patients, which may be more pronounced among bipolar I patients, and of relevance for the pathophysiology of the disorder.

Adult↗

Perspectives on the use of anticonvulsants in the treatment of bipolar disorder.

The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.

Anticonvulsants↗

Differential effects of age on brain gray matter in bipolar patients and healthy individuals.

This study examined possible differences in total gray and white matter brain content in bipolar patients and healthy individuals, and their relationship with age. 22 DSM-IV bipolar patients and 22 healthy controls underwent a 1.5-tesla Spoiled Gradient Recalled Acquisition (SPGR) MRI. Evaluators blind to patients' identities measured total brain, gray and white matter volumes using a semi-automated software. No differences were found for total brain volume, gray matter or white matter volumes between bipolar patients and healthy controls (MANCOVA, age as covariate, p > 0.05). Age was inversely correlated with total gray matter volume in patients (r = -0.576, p = 0.005), but not in controls (r = -0.193, p = 0.388). Our findings suggest that any existing gray matter deficits in bipolar disorder are likely to be localized to specific brain regions, rather than generalized. The inverse correlation between age and brain gray matter volumes in bipolar patients, not present in healthy controls, in this sample of mostly middle-aged adults, could possibly indicate more pronounced age-related gray matter decline in bipolar patients, and may be of potential relevance for the pathophysiology of the disorder.

Adolescent↗