Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell

CD5(+) diffuse large B-cell lymphomas (DLBLs) have recently been described as a particular subgroup of DLBLs. Classical banding and interphase cytogenetic analyses targeting ATM, TP53, and P16(INK4a) genes and the D13S25 locus from 13 CD5(+) DLBLs were compared with 55 CD5(-) DLBLs. Additionally, analysis of somatic mutations of the immunoglobulin heavy chain variable region (IgVH) genes were performed in CD5(+) DLBLs. CD5(+) DLBLs were somatically mutated (7 of 8 cases) and were negative for t(11;14)(q13;q32) and t(14;18)(q32;q21), whereas t(3;14)(q27;q32) was found in only one tumor. Trisomy 3 and gains on chromosomes 16/16p and 18/18q were significantly overrepresented in CD5(+) DLBLs. No ATM deletions were detected. The prevalence of deletions at the D13S25 locus was significantly higher in CD5(+) DLBLs (4 of 12 [33%]) compared with CD5(-) DLBLs (4 of 42 [10%]), as were p16(INK4a) deletions (33% versus 8%). On the basis of these findings, CD5(+) DLBLs are likely to arise from the same progenitor cell as the mutated variant of CD5(+) lymphocytic lymphoma/B-cell chronic lymphocytic leukemia (B-CLL).     

A randomized, double-blind, placebo-controlled study of sibutramine in the treatment of binge-eating disorder

BACKGROUND: Although antidepressants are the pharmacological agents most often studied in the treatment of binge-eating disorder (BED), preliminary evidence from an open trial suggests that the antiobesity agent sibutramine hydrochloride may be effective. The objective of this study was to evaluate the efficacy and tolerability of sibutramine in obese patients with BED. METHODS: After a 2-week run-in period, 60 obese outpatients (body mass index [calculated as weight in kilograms divided by the square of height in meters] 30-45), who met DSM-IV criteria for BED were randomly assigned to receive sibutramine hydrochloride (n = 30), 15 mg/d, or placebo (n = 30) in a 12-week double-blind study at 2 centers. The primary outcome measure was binge frequency, expressed as the number of days with binge-eating episodes during the past week. Secondary outcome measures included Binge Eating Scale, Beck Depression Inventory scores, weight, and treatment responder status (remission and response). For each efficacy outcome, an intent-to-treat analysis was performed using random regression methods. RESULTS: There was a significant reduction in the number of days with binge episodes in the sibutramine group compared with the placebo group (t203 = 2.14; P =.03); this was associated with an important and significant weight loss (-7.4 kg) compared with a small weight gain in the placebo group (1.4 kg) (t147 = 4.88; P<.001). Sibutramine was also associated with a significantly greater rate of reduction in Binge Eating Scale (t202 = 3.64; P<.001) and Beck Depression Inventory (t201 = 3.72; P<.001) scores. Dry mouth (P =.01) and constipation (P<.001) were more common adverse reactions with sibutramine than placebo. CONCLUSIONS: Sibutramine is effective and well tolerated in the treatment of obese patients with BED. Its effects address 3 main domains of the BED syndrome, ie, binge eating, weight, and related depressive symptoms.     

Prenatal choline deficiency decreases the cross-sectional area of cholinergic neurons in the medial septal nucleus

Levels of dietary choline in utero influence postnatal cognitive performance. To better understand this phenomenon, forebrain cholinergic neurons were studied in the 8-9 month old offspring of dams fed a control or choline-deficient diet from EDs 11-17. Serial sections were immunostained with antibodies against p75, a cholinergic marker. Neuronal morphology was analyzed in the basal forebrain, a heterogeneous area composed of several structures including the medial septal nucleus (MSN), nucleus of the diagonal band (DB), and the nucleus basalis of Meynert (NB). Neuronal cross-sectional areas were selectively reduced in the MSN of choline-deficient animals, compared to controls, but cell counts were not altered. Our findings suggest that cholinergic medial septal neurons may be selectively vulnerable to in utero choline deficiency.     

Attention-deficit-hyperactivity disorder with and without oppositional defiant disorder in 3- to 7-year-old children

Attention-deficit-hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a high degree of associated behavioural problems. In order to study characteristics of ADHD with and without oppositional defiant disorder (ODD) in a representative group of young children with clinical impairment in Sweden, 131 children (101 males, 30 females) with ADHD (mean age 5 years, SD 1 year 5 months; range 3 to 7 years) were clinically examined, and their parents interviewed. Independent questionnaire data (Child Behavior Checklist, ADHD Rating Scale-IV, ODD Rating Scale-IV, Conners Hyperactivity Index) were collected. For comparison 131 children without ADHD were matched for sex, age, marital status, and socioeconomic status (115 males, 16 females; mean age 4 years 10 months, SD 1 year 5 months; range 3 to 7 years). Sixty percent of those with ADHD met full DSM-IV criteria for ODD. Only 10 of the 131 children with ADHD had no symptoms of ODD at all. The rate of children meeting full diagnostic criteria for ODD was similar across all age cohorts. Males were overrepresented in ODD, as were children of divorced parents and of mothers with low socioeconomic status. ADHD combined subtype was a stable independent factor influencing the diagnosis of ODD, regardless of psychosocial factors. Those with ADHD with ODD consistently showed higher rates of ADHD symptoms than did those with ADHD without ODD. The prevalent comorbidity of ADHD with ODD indicates that all children presenting with ADHD or ODD symptoms need to be assessed with a view to exploring both types of problem behaviours. The link between ODD and some psychosocial variables indicates the need to address these, possibly by measures such as parent training and network support.     

A study of 43 patients with panayiotopoulos syndrome,a common and benign childhood seizure susceptibility

PURPOSE: To determine prevalence, clinical, EEG features, and prognosis of Panayiotopoulos syndrome and to examine the proposition that clinical manifestations are more important than EEG findings. METHODS: We analyzed retrospectively the clinical and EEG records of 1,340 children with one or more focal seizures seen in the last 18 years, supplemented with a prospective study from 1998. Panayiotopoulos syndrome was defined by clinical criteria, mainly ictal emesis, irrespective of EEG findings. RESULTS: We analyzed 43 of 90 patients with Panayiotopoulos syndrome who were seizure free >2 years. Girls predominated. Mean age at first seizure was 5 years. Seizures consisted mainly of autonomic manifestations; ictal emesis was often the first symptom, culminating in vomiting in 86%. Of nonautonomic manifestations, lateral eye deviation was the most common; visual symptoms were exceptional. Impairment of consciousness ensued in all seizures, half of which ended with hemi or generalized convulsions. Nearly 46.5% of cases had at least one seizure >30 min, constituting autonomic status epilepticus. Seizures during sleep (84%) were more common than those in wakefulness. EEG showed occipital spikes in 29 patients. Of the other 14 cases, five had extraoccipital abnormalities or brief generalized discharges, and nine had normal awake and sleep EEG. Prognosis was excellent. All 43 children have been free of seizures for > or =2 years, 53% having a single seizure, and 47%, an average two to three seizures. CONCLUSIONS: Panayiotopoulos syndrome is common and needs wider recognition. EEG shows occipital or extraoccipital abnormalities, is normal in one third of patients, and does not determine clinical manifestations or prognosis, which is excellent despite the high prevalence of lengthy seizures.