Accurate topographical diagnosis of urinary tract infection in male patients with (111)indium-labelled leukocyte scintigraphy

Background: Although the clinical diagnosis of urinary tract infection (UTI) is straightforward, the precise localization of the urogenital organ affected by the infection is often difficult to establish. Methods: To evaluate this, we prospectively studied 20 males with a clinical diagnosis of acute pyelonephritis (APN), acute prostatitis (AP) and febrile UTI (FUTI), as well as seven control females with APN. (111)Indium-labelled leukocyte scintigraphy (ILS) was performed during the febrile episode and repeated when patients were free of symptoms. Results: ILS showed an abnormal uptake in a urinary organ in every case. All patients with AP showed uptake in the pelvic area. Four male patients presented AP, one of them had uptake in the lumbar area, one in the lumbar and pelvic area, and two in the area of the prostate only. Six out of seven patients with FUTI presented uptake in the pelvic area. All female patients showed kidney uptake. After the clinical resolution of the UTI, no residual uptake was found in any case except for one. Conclusions: These results suggest that ILS is very useful in localizing the affected organ in febrile UTI. Most male patients with a febrile UTI presented a prostatic involvement, suggesting that many cases of APN or FUTI in males may actually be cases of AP not recognized by standard clinical evaluation.     

In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride

(-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D2 receptor agonist and [11C]NPA is a suitable radiotracer to image D2 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic DA was assessed with PET in baboons and compared to that of the reference D2 receptor antagonist radiotracer [11C]raclopride. Three male baboons were studied with [11C]raclopride and [11C]NPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg(-1) i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific-to-nonspecific equilibrium partition coefficient (V3"). [11C]Raclopride V3" was reduced by 24 +/- 10%, 32 +/- 6%, and 44 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. [11C]NPA V3" was reduced by 32 +/- 2%, 45 +/- 3%, and 53 +/- 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg(-1), respectively. Thus, endogenous DA was more effective at competing with [11C]NPA binding compared to [11C]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [11C]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease.     

Theta reset produces optimal conditions for long-term potentiation

Connections among theta rhythm, long-term potentiation (LTP) and memory in hippocampus are suggested by previous research, but definitive links are yet to be established. We investigated the hypothesis that resetting of local hippocampal theta to relevant stimuli in a working memory task produces optimal conditions for induction of LTP. The timings of the peak and trough of the first wave of reset theta were determined in initial sessions and used to time stimulation (4 pulses, 200 Hz) during subsequent performance. Stimulation on the peak of stimulus-reset theta produced LTP while stimulation on the trough did not. These results suggest that a memory-relevant stimulus produces a phase shift of ongoing theta rhythm that induces optimal conditions for the stimulus to undergo potentiation.     

Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study

Based on the putative relationship between depleted omega-3 fatty acids and postpartum depression, we initiated an open-label pilot study of omega-3 fatty acid supplementation with the aim of preventing postpartum depression. Euthymic pregnant females with a past history of depression in the postpartum period were started on 2960 mg of fish oil (1.4:1 eicosapentaenoic acid:docosahexaenoic acid) per day between the 34th to 36th week of pregnancy and assessed through 12 weeks postpartum. Four of seven participants had a depressive episode during the study period. No participants withdrew from the study due to adverse events. This preliminary, small, open-label pilot study failed to show promising results for the use of omega-3 fatty acid monotherapy beginning at 34 to 36 weeks gestation for the prevention of postpartum depression in patients with a prior postpartum depression history. Controlled studies are lacking.     

Lamotrigine treatment of bipolar disorder: data from the first 500 patients in STEP-BD

Objective:  To describe the frequency and correlates of lamotrigine therapy among the first 500 patients enrolled into the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study.
Method:  Systematic recording of psychiatric history and medication data at intake into the STEP-BD project.
Results:  Of the participants with bipolar disorder type I or II (n = 483), 77 (15.4%) were currently taking lamotrigine (mean dose: 258.12 mg/day) and 52 (10.4%) reported prior lamotrigine use. The groups were comparable with regard to duration of illness and mood state at study entry. Compared with participants who had never taken lamotrigine, those currently treated with lamotrigine were significantly more likely to have a prior history of rapid cycling (62.5% vs. 43.1%; p < 0.01) and an antidepressant-induced switch to (hypo)mania (49.3% vs. 33.3%; p < 0.01). In contrast, only 16.9% of lamotrigine-treated participants were taking an antidepressant at study intake, as compared with 29.1% of participants with no history of lamotrigine therapy (p < 0.03).
Conclusions:  While noting the limitations of a cross-sectional assessment, these data suggest that lamotrigine therapy was commonly used in these academic centers for patients with bipolar disorder several years before it was recommended in the American Psychiatric Association practice guidelines, particularly in patients with a history of rapid cycling or antidepressant-induced mania.     

Assessment of the bioactivity of antibodies against beta-amyloid peptide in vitro and in vivo

The accumulation of the beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). Abeta removal from the brain by immune therapy shows promising potential for the treatment of patients with AD, although the mechanisms of the antibody action are incompletely understood. In this study we compared the biological activities of antibodies raised against various Abeta fragments for Abeta reduction in vitro and in vivo. Antibodies against Abeta enhanced the uptake of Abeta42 aggregates up to 6-fold by primary microglial cells in vitro. The kinetics of Abeta42 uptake varied considerably among antibodies. Based on the activity to mediate Abeta42 uptake by microglial cells, we identified a bioactive antibody that significantly reduced Abeta42 levels in the brains of transgenic mice with neuronal expression of an AD-related mutated amyloid precursor protein. This effect depended on the epitopes recognized by the antibody. Our data suggest that the ability to facilitate Abeta42 uptake by primary microglia cells in vitro can be used to predict the biological activity of the antibody by passive immunization in vivo. This protocol may prove useful for the rapid validation of the activity of antibodies designed to be used in immune therapy of AD.     

Complicated grief in Bosnian refugees: associations with posttraumatic stress disorder and depression

Complicated grief is likely to be common among refugee populations exposed to war trauma. However, there have been few studies investigating the traumatic antecedents and correlates of complicated grief in refugees, and the relationship of that symptom pattern with other common disorders such as posttraumatic stress disorder (PTSD) and depression. We studied Bosnian refugees recruited from a community center in Sydney, Australia, with the sample being supplemented by a snowball method (N = 126; response rate, 86%). Measures included a trauma inventory, the Clinician Administered PTSD Scale (CAPS), the depression module of the Structured Clinical Interview (SCID), and the Core Bereavement Items (CBI). A dimension of traumatic loss derived from the trauma inventory was a specific predictor of complicated grief, with exposure to human rights violations being associated with images of the traumatic events surrounding the lost person. There was no link between PTSD and grief other than for a low-order association with the PTSD intrusion dimension. In contrast, depression was strongly associated with grief and its subscales. Only the subgroup with comorbid grief and depression reported higher levels of traumatic loss. The results suggest that complicated grief in refugees can become persistent and associated with depression. While PTSD and grief share common symptoms of intrusion, the two symptom domains are sufficiently distinct to warrant independent assessment of grief in refugee populations.     

Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. The presence of mutations in the superoxide dismutase gene (SOD1) has led to theories regarding a role for oxidative stress in the pathogenesis of this disease. A primary cause of oxidative stress is perturbations in cellular iron homeostasis. Cellular iron mismanagement and oxidative stress are associated with a number of neurodegenerative diseases. One mechanism by which cells fail to properly regulate their iron status is through a mutation in the Hfe gene. Mutations in the Hfe gene are associated with the iron overload disease, hemochromatosis. In the current study, 31% of patients with sporadic ALS carried a mutation in the Hfe gene, compared to only 14% of patients without identifiable neuromuscular disease, or with neuromuscular diseases other than ALS (p<0.005). To determine the cellular consequences of carrying an Hfe mutation, a human neuronal cell line was transfected with genes carrying the Hfe mutation. The presence of the Hfe mutation disrupted expression of tubulin and actin at the protein levels potentially consistent with the disruption of axonal transport seen in ALS and was also associated with a decrease in CuZnSOD1 expression. These data provide compelling evidence for a role for the Hfe mutation in etiopathogenesis of ALS and warrant further investigation.     

A novel system for the determination of antidepressant concentrations in human breast milk

The high incidence of psychiatric illness in the postpartum period and the increasing percentage of women who breastfeed has focused attention on the treatment of breastfeeding women with psychotropic medications and, additionally, the exposure of nursing infants to these medications. Consequently, there has been an increased effort to develop standardized methods for quantifying psychotropic medications in breast milk. This paper details a novel method for quantifying the concentrations of multiple selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in breast milk. The method consists of a common liquid/liquid and solid-phase extraction followed by HPLC separation on a common column and UV detection. Assay system 1 measures fluoxetine, norfluoxetine, fluvoxamine, and paroxetine; assay 2 measures sertraline and desmethylsertraline; and assay 3 measures the TCAs including doxepin, nordoxepin, desipramine, imipramine, nortriptyline, and amitriptyline. The method is shown to be a highly accurate and precise technique for measuring 12 different antidepressants in human breast milk and to be free of the matrix effects often encountered in breast milk drug analyses.