5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression.

The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or L(G)) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.     

Tracker-assisted laser in situ keratomileusis for myopia using the autonomous scanning and tracking laser: 12-month results

OBJECTIVE: To determine the safety, efficacy, and predictability of the Autonomous scanning and tracking laser for the correction of myopia and myopic astigmatism with laser in situ keratomileusis (LASIK) procedure. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The first 129 consecutive eyes with up to -13.00 diopters (D) of myopia and -5.00 D of astigmatism. INTERVENTION: Myopic tracker-assisted LASIK (T-LASIK) using the Autonomous Laser (Alcon Summit Autonomous, Waltham, MA) and Hansatome microkeratome (Bausch & Lomb Surgical, Bracknell, England). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), manifest spherical equivalent (MSE), best spectacle-corrected visual acuity (BSCVA), and complications were studied. RESULTS: At 12 months, the mean MSE was -0.02 +/- 1.01 D, with 79.1% of eyes within 0.5 D and 89.9% of eyes within 1 D of the intended correction. UCVA was 20/20 or better in 71.4%, 20/25 or better in 78.5%, and 20/40 or better in 92.8% of eyes. Two eyes (1.6%) lost 2 lines and five eyes (3.8%) gained 2 lines of BSCVA. Sixteen eyes (12.4%) required retreatment to correct residual myopia or astigmatism. After retreatment, 14 of 16 eyes were within 0.5 D of emmetropia. Nine eyes (6.9%) had minor flap complications; two eyes (1.6%) had grade 2 diffuse lamellar keratitis, of which one eye had associated peripheral flap melt. One eye showed slight decentration; this eye was rolling throughout the procedure. All eyes had some dryness, with 10% severe enough to require temporary punctual occlusion with plugs. CONCLUSIONS: T-LASIK for myopic astigmatism with the Autonomous Laser is relatively safe, effective, and predictable. The tracker seems to be effective, and the complications are relatively few. Retreatment rates are acceptable and can be performed safely and effectively to improve visual outcome. The outcomes are comparable with other published data.     

Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions

In the search for improved selective antagonist ligands of the A2B adenosine receptor, which have the potential as antiasthmatic or antidiabetic drugs, we have synthesized and screened a variety of alkylxanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions. Competition for 125I-ABOPX (125I-3-(4-amino-3-iodobenzyl)-8-(phenyl-4-oxyacetate)-1-propylxanthine) binding in membranes of stably transfected HEK-293 cells revealed uniformly higher affinity (<10-fold) of these xanthines for human than for rat A2B adenosine receptors. Binding to rat brain membranes expressing A1 and A2A adenosine receptors revealed greater A2B selectivity over A2A than A1 receptors. Substitution at the 1-position with 2-phenylethyl (or alkyl/olefinic groups) and at N-3 with hydrogen or methyl favored A2B selectivity. Relative to enprofylline 2b, pentoxifylline 35 was equipotent and 1-propylxanthine 3 was >13-fold more potent at human A2B receptors. Most N-7 substituents did not enhance affinity over hydrogen, except for 7-(2-chloroethyl), which enhanced the affinity of theophylline by 6.5-fold to 800 nM. The A2B receptor affinity-enhancing effects of 7-(2-chloroethyl) vs 7-methyl were comparable to the known enhancement produced by an 8-aryl substitution. Among 8-phenyl analogues, a larger alkyl group at the 1-position than at the 3-position favored affinity at the human A2B receptor, as indicated by 1-allyl-3-methyl-8-phenylxanthine, with a K(i) value of 37 nM. Substitution on the 8-phenyl ring indicated that an electron-rich ring was preferred for A2B receptor binding. In conclusion, new leads for the design of xanthines substituted in the 1-, 3-, 7-, and 8-positions as A2B receptor-selective antagonists have been identified.     

C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984-1998

BACKGROUND: Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. OBJECTIVE: To investigate the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men. METHODS: A total of 2052 initially nondiabetic men aged 45 to 74 years who participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire mailed to participants in 1998. High-sensitive CRP was measured by an immunoradiometric assay. RESULTS: A total of 101 cases of incident diabetes occurred during the follow-up period. The age-standardized incidence rate was 6.9 per 1000 person-years. Men with CRP levels in the highest quartile (CRP > or = 2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence interval, 1.4-5.2) compared with men in the lowest quartile (CRP < or = 0.67 mg/L) in a Cox proportional hazards model adjusted for age and survey. After further adjustment for body mass index, smoking, and systolic blood pressure, the observed association was significantly reduced and became nonsignificant. CONCLUSIONS: Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus in middle-aged men. Inflammation could be one mechanism by which known risk factors for diabetes mellitus, such as obesity, smoking, and hypertension, promote the development of diabetes mellitus.     

Rats recovering from unilateral barrel-cortex ischemia are capable of completing a whisker-dependent task using only their affected whiskers

Rats use their vibrissae for a variety of exploratory tasks including location of objects and discrimination of texture. This study examines recovery in vibrissal function following a unilateral ischemic injury to the somatosensory cortex. Vibrissal function was examined in adult food-restricted rats performing on a two-texture discrimination device. Animals were trained and tested until the criteria of >80% correct choices was demonstrated on three consecutive days. Ischemic rats were constrained to use the affected whiskers by clipping the ipsilateral vibrissae. One group was tested after ischemia, a second group was trained before ischemia and then tested, and a third group was pre-trained and received whisker stimulation and tested post-ischemia. Nai;ve animals recovering from ischemia took longer to reach criteria than intact or unilateral trimmed control animals. Pre-trained animals with compression ischemia receiving whisker stimulation with sucrose water completed the task to criteria in the fewest number of trials. The results indicate that recovery of vibrissal function occurs following a unilateral ischemic injury. Histological analysis in animals without whisker stimulation indicates that the number of normal appearing cortical barrels following ischemia was inversely correlated to the number of trials needed to complete the behavioral task. This suggests that the natural recovery of the ability to discriminate textures is related to the degree of damage to the barrel cortex. The relationship between cortical barrels and behavioral recovery did not hold for the ischemic animals receiving whisker stimulation. This latter group demonstrated recovery despite marked anatomical lesions suggesting that the intervention influenced reorganization.     

Epileptic spasms and partial seizures as a single ictal event

PURPOSE: To investigate the phenomenon of epileptic spasms (ESs) associated with other seizure types in a single ictal event and to study the predictive value of this phenomenon regarding etiology and prognosis. METHODS: We selected retrospectively eight female and five male patients, who had ESs and other seizure types within a single seizure event and for whom a video-EEG recording of the phenomenon was performed in at least one situation. RESULTS: The seizure type associated with ESs was a partial seizure in all patients. We identified three groups with different seizure patterns regarding the temporal association of ES and partial seizures (PSs): (a) PS followed by ES; (b) PS appearing during a cluster of ESs without interrupting the cluster; and (c) complex seizure interaction with a succession of ESs and PSs in a close but variable temporal association. Underlying disorders included cortical dysplasia (three patients), complex cerebral malformations (two patients), and perinatal anoxic-ischemic injuries (two patients); four cases were classified as cryptogenic, and in two children, etiology was unknown, but prenatal origin was suspected. Outcome was poor in nine cases with intractable epilepsy; four cases had a favorable outcome, defined as complete cessation of epileptic seizures. CONCLUSIONS: The phenomenon of associated ESs and PSs as a single ictal event can be related to different etiologies and should not be considered distinctive for cortical malformations or severe brain damage. Different seizure patterns of associated ESs and PSs provide no hint for etiology or prognosis. Outcome is prevalently but not constantly unfavorable in patients with the phenomenon.     

"Beware of coming too close to me"--development-oriented psychotherapy of a dangerous aggressive boy with early complex trauma experiences

Early maltreatment of children can lead to severe disorders in the regulation of behaviour and affect, alterations in awareness and distorted perception. In development-oriented psychotherapy, therapeutic interventions which are directed to regulating processes, decentration or mentalization, desomatization and symbolization of enacted messages play a central role. The results of early traumatization and of therapeutic interventions are portrayed, examining the multi-dimensional diagnosis and therapy of a dangerously aggressive 12-year-old boy as an example. From this, it becomes clear how, through new experiences with regulating others, he gradually surfaces from a world of annihilation and destruction and learns to survive and to live.