A Prospective Open‐Label Trial of Lamotrigine Monotherapy in Children and Adolescents with Bipolar Disorder

Aim: To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. Method: This was a 12‐week, open‐label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions‐Improvement scale (CGI‐I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self‐reports, vital signs weight monitoring, and laboratory analysis. Results: Thirty‐nine children with bipolar disorder (YMRS at entry: 31.6 ± 5.5) were enrolled in the study and 22 (56%) completed the 12‐week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 ± 128.3 in subjects <12 years of age (N = 22) and 219.1 ± 172.2 mg/day in children 12–17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (?14.9 ± 9.7, P < 0.001) at endpoint. Lamotrigine treatment also resulted in significant improvement in the severity of depressive, attention‐deficit/hyperactivity disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 ± 18.0 kg vs. 47.2 ± 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Conclusions: Open‐label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo‐controlled, double‐blind studies are warranted to confirm these findings.     

Repetition-related reductions in neural activity reveal component processes of mental simulation

In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal–parietal–temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal–parietal–temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g. medial prefrontal, posterior cingulate, temporal–parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.     

Bradycardia without associated hypertension: a common sign of ventriculo-peritoneal shunt malfunction

Introduction  

Delayed diagnosis of ventriculo-peritoneal (VP) shunt malfunction results in avoidable morbidity and mortality. One reason is that most of the signs of shunt malfunction have low specificity.     

Upper eyelid extension of a filtering bleb following glaucoma shunt surgery.

The authors describe a case of a filtering bleb that extended into the eyelid of a 71-year-old man following glaucoma surgery with a shunt implant. The patient presented with a left upper eyelid mass and had ocular surface and mechanical sequelae. Computed tomography scan demonstrated a fistula between the original filtering tract and the eyelid, creating an inadvertent filtering bleb. Cytology revealed fluid consistent with aqueous humor. Intraocular pressure remained normal and symptoms improved with conservative management. The patient deferred any surgical revision. Glaucoma tube shunts may lead to ocular and rare orbital complications from inadvertent bleb extension, as seen in this case.     

Normal flora: living vehicles for non-invasive protein drug delivery

Feasibility to use probiotic bacteria as a living protein delivery system through oral route was assessed in vitro. Lactococcus lactis transformed with a plasmid to express and secret beta-lactamase was used to deliver beta-lactamase through Caco-2 monolayer, an intestine epithelium. Transport of beta-lactamase through Caco-2 monolayer was carried out in the transwells. The viability and integrity of the cell monolayers co-cultured with L. lactis was examined by trypan blue exclusion method and by measuring the transport of mannitol and propranolol as well as the transepithelial electrical resistance (TEER). Results show that it is feasible to use cell culture technique to evaluate the drug delivery by normal flora. The transport rate of beta-lactamase when delivered by L. lactis was 2.0 +/- 0.1 x 10(-2)h(-1) (n = 9) and through free solution form was 1.0 +/- 0.1 x 10(-2)h-1. When co-cultured with L. lactis, Caco-2 cell viability decreased to 98, 96, and 94% at 6, 8, and 10h, respectively. Transport of mannitol through Caco-2 cell monolayer was significantly increased and the transport of propranolol through Caco-2 cell monolayer was significantly decreased in the presence of L. lactis. Increase in the amount of protein delivered is probably due to the concentrate of the protein by L. lactis on the monolayer (absorption surface) and the opening of the tight junction of Caco-2 monolayer by L. lactis.     

Stimulation site determines the conditioned effects of kindling in rats: anterior neocortex versus amygdala

Rats received 53 stimulations to either the left basolateral amygdala (BA) or left anterior neocortex (AN) in one environment (CS+) and 53 sham stimulations (the stimulation lead was attached but no current was delivered) in another environment (CS-), quasirandomly over 54 days. Confirming a previous report [Barnes, S.J., Pinel, J.P., Francis, L.H. & Wig, G.S. (2001) Behav. Neurosci., 115, 1065-1072], as BA kindling progressed, the CS+ began to elicit more defensive behaviours (i.e. less activity, more freezing and avoidance of the CS+) than the CS-, and at the end of the experiment, convulsions elicited in the CS+ were more severe than those elicited in the CS-. Like BA kindling, AN kindling led to less activity in the CS+; but unlike BA kindling, AN kindling led to more wet-dog-shakes and less, rather than more, severe convulsions in the CS+. During AN kindling, the mean number of wet-dog-shakes in the CS+ was negatively correlated with the mean convulsion class, suggesting that wet-dog-shakes contribute to the inherent variability of AN kindling. These findings confirm that inherent conditioned effects influence kindled convulsions and interictal behaviour and establish for the first time that the pattern of these conditioned effects is a function of the kindling site.