Neural correlates of aversive conditioning: development of a functional imaging paradigm for the investigation of anxiety disorders

The purpose of the present study was to establish a short paradigm for the examination of classical aversive conditioning processes for application in patients with anxiety disorders. We measured behavioral, autonomic and neural correlates of the paradigm in healthy subjects, applying functional magnetic resonance imaging (fMRI) and measurement of skin conductance. Therefore, neutral visual stimuli were paired with an unpleasant white noise as unconditioned stimulus. Twenty healthy subjects performed three experimental phases of learning: familiarization, acquisition and extinction. Subjective ratings of valence and arousal after each phase of conditioning as well as skin conductance measurement indicated successful conditioning. During acquisition, fMRI results showed increased activation for the conditioned stimulus (CS+_unpaired) when compared with the non-conditioned stimulus (CS−) in the right amygdala, the insulae, the anterior cingulate cortex and the parahippocampal gyrus, all regions known to be involved in emotional processing. In addition, a linearly decreasing activation in the right amygdala/hippocampus for the CS− across the acquisition phase was found. There were no significant differences between CS+ and CS− during extinction. In conclusion, the applicability of this paradigm for the evaluation of neural correlates in conditioning and extinction processes has been proven. Thus, we present a promising paradigm for the examination of the fear-circuit in patients with anxiety disorders and additionally effects of cognitive-behavioral interventions.     

Altered amygdala functional connectivity in adult Tourette's syndrome

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Recently, differences in maturation of cortical networks using functional connectivity metrics have been described for this disorder. However, adult data on subcortical networks are scarce. In particular, the connectivity of the amygdala, for which a role in the pathophysiology of TS has been established, has not been examined so far. We studied 15 adult TS patients (11 male, aged 30.4 ± 9.7y) and 15 age- and sex-matched controls (11 male, aged 32.0 ± 9.3y) in a functional magnetic resonance imaging study at 1.5T using a simple motor task. We corrected for possible confounds introduced by tics, motion and brain-structural differences as well as age, sex, and medication. Task performance was monitored by simultaneous MR-compatible video-recording. Data were analyzed using an independent component approach sensitive to functional connectivity patterns. A stable component comprising both amygdalae could be identified across all subjects. Additionally, we observed a highly significant increase in coupling between/within amygdalae in the TS group when compared to controls, although behavioral data obtained during scanning did not show significant differences. These findings are expected to add to our understanding of the functional architecture of Tourette's syndrome.     

Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.     

Anxiety sensitivity correlates with two indices of right anterior insula structure in specific animal phobia

Background: Anxiety sensitivity (AS) is a dispositional trait involving fear of anxiety‐related symptoms. Functional imaging research suggests that the activity of the anterior insular cortex, particularly the right insula, may both mediate AS and play a role in the pathophysiology of phobias. However, no imaging studies have examined whether AS relates to insula morphology. We examined whether AS was significantly correlated with right anterior insula volume and thickness among adults with specific animal phobia (SAP) and healthy comparison (HC) subjects. Methods: Nineteen adults with SAP and 20 demographically group‐matched HC subjects underwent magnetic resonance imaging at 3 Tesla. Subjects also completed the Anxiety Sensitivity Index (ASI). Regression and correlation analyses examined ASI scores in relation to anterior and posterior insular cortex volume and thickness within and across subject groups. Results: SAP subjects had significantly higher ASI scores than HC, but did not differ in terms of insula volumes or thickness. ASI scores predicted right anterior insula thickness in SAP but not HC subjects, and right anterior insula volume in the sample as a whole. Correlations of ASI scores with the anterior and posterior insula volume and thickness were not significant in either group. Conclusions: These findings suggest that the right anterior insular cortex size is a neural substrate of AS within specific phobia, rather than an independent diagnostic marker of the disorder. Future investigations should examine whether heightened AS represents a shared intermediate phenotype across anxiety disorders, manifesting functionally as increased insular reactivity and clinically as a fear of anxiety symptoms. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging

BACKGROUND: The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is a malformation of the female genitals (occurring in one in 4000 female live births) as a result of interrupted embryonic development of the Müllerian (paramesonephric) ducts. This retrospective study examined the issue of associated malformations, subtyping, and the frequency distribution of subtypes in MRKH syndrome. METHODS: Fifty-three MRKH patients were investigated using a newly developed standardized questionnaire. Together with the results of clinical and diagnostic examinations, the patients were classified into the three recognized subtypes [typical, atypical and MURCS (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia)]. RESULTS: The typical form was diagnosed in 25 patients (47%), the atypical form in 11 patients (21%), and the most marked form-the MURCS type-in 17 patients (32%). Associated malformations were notably frequent among the patients. Malformations of the renal system were the most frequent type of accompanying malformation, with 23 different malformations in 19 patients, followed by 18 different skeletal changes in 15 patients. CONCLUSIONS: In accordance with the literature, this study shows that associated malformations are present in more than a third of cases. Therefore, new basic guidelines for standard diagnostic classification involving patients with suspected MRKH are presented.     

Autoimmune pancreatitis associated with a large pancreatic pseudocyst

INTRODUCTIONAutoimmune pancreatitis (AIP) is a benign disease that responds well to steroid treatment. Characteristics in-clude radiological evidence of an irregular narrowing of the pancreatic main duct and a diffuse enlargement of the pancreas, together…     

Intraoperative brain ultrasound: a new approach to study flow dynamics in intracranial aneurysms

The aim was to evaluate the potential of contrast-enhanced ultrasound to visualize the hemodynamics in intracranial aneurysms during neurosurgical intervention and to quantify the ultrasound data using digital particle image velocimetry (DPIV) technique. Aneurysms were scanned through the intact dura mater, preclipping and again postclipping after closure of the dura. After intravenous injection of Optison, angio-like views of the vascular tree surrounding the aneurysm, including the aneurysm sac, were obtained. Single ultrasound contrast agent microbubbles could be visualized in the aneurysm sac and the flow dynamics could be assessed in vivo. Spatial and temporal distributions of the velocity in the aneurysm and in the parent vessels were measured with DPIV using the backscattered signals from the microbubbles. Subsequently, the fluid stresses, vorticity, circulation, etc., were calculated from the velocity fields. We demonstrate in this paper that intraoperative contrast-enhanced ultrasound can be used to quantify the flow dynamics within an aneurysm.     

A comparison of three-dimensional ultrasound, two-dimensional ultrasound and dissections for determination of lesion volume in tendons

The purpose of this work was to evaluate the accuracy and precision of a freehand three-dimensional (3-D) ultrasonography system in the determination of lesion volume in tendons. The accuracy and precision of a 3-D ultrasonography system was assessed by performing repeated measurements on a phantom of known volume. Volume measurements of tendon lesions performed with 3-D ultrasonography were compared with measurements based on a series of two-dimensional (2-D) ultrasound (US) scans and to direct measurements from dissections. A novel method for the creation of tendon lesions in vitro was developed. 3-D US showed excellent precision and accuracy in measurements of the phantom (mean measured volume = 3.76 mL, calculated volume = 3.77 mL, coefficient of variation (CoV) = 0.54%) and good repeatability in the determination of tendon lesions (repeatability coefficient = 0.00047). All three methods examined were repeatable (repeatability coefficient for 2-D US = 0.00032, repeatability coefficient for dissections = 0.00076). However, each of the methods produced different results and no constant relationship could be found between any of the measurement methods. Both 3-D and 2-D US proved to be repeatable techniques for the measurement of the volume of a tendon lesion. Even if they produced different results, each of them can be repeatedly used individually. It was not possible to define which one provided the most accurate value as a result of difficulties encountered in lesion identification on histology, and therefore the lack of a gold standard.     

Nonsurgical treatment of moderate and advanced periimplantitis lesions: a controlled clinical study

The aim of this controlled, parallel design clinical study was to evaluate the effectiveness of an Er:YAG (erbium-doped:yttrium, aluminum, and garnet) laser for nonsurgical treatment of periimplantitis lesions. Twenty patients, each of whom displayed at least one implant with (a) moderate and (b) advanced periimplantitis (n=40 implants; IMZ, ITI, Spline Twist, ZL-Duraplant, Camlog), were randomly instrumented nonsurgically using either (1) an Er:YAG laser (100 mJ/pulse, 10 Hz) device (LAS) or (2) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate (0.2%) (C). The following clinical parameters were measured at baseline, 3, 6, and 12 months after treatment: plaque index, bleeding on probing (BOP), probing depth, gingival recession, and clinical attachment level (CAL). Mean BOP improved significantly in both groups at 3, 6, and 12 months (a− lesions: P<0.001 and b− lesions: P<0.01, respectively). After 3 and 6 months, the mean reduction of BOP was significantly higher in the LAS group when compared to the C group (a− and b− lesions: P<0.01 and P<0.05, respectively). At 3 and 6 months, both groups revealed significant CAL gains at a− and b− lesions (P<0.01, respectively). In both groups, however, the mean CAL at a− and b− lesions was not significantly different from the respective baseline values at 12 months (P>0.05, respectively). Although treatment of periimplantitis lesions with LAS resulted in a significantly higher BOP reduction than C, its effectiveness seemed to be limited to a period of 6 months, particularly at b− lesions.     

Firearm-related personal and clinical characteristics of US medical students

BACKGROUND: Firearm injuries are the second leading cause of fatal injury in the US, and several medical specialty societies encourage patient counseling about firearm injury prevention. Because personal choices. influence physicians' willingness to counsel, it would be valuable to know how frequently guns are kept in the homes of physicians-in-training, as well as their perceptions and current rates of counseling about firearm injury prevention. METHODS: At a nationally representative sample of 16 medical schools, we surveyed the class of 2003 at freshman orientation, entrance to wards, and during senior year. RESULTS: A total of 2,316 students provided data (response rate = 80.3%). Among freshmen, 16% reported living in a home with a firearm, 13% did so at entry to wards, as did 14% of seniors (14% overall, women = 9%, men = 19%). Only 34% of seniors reported counseling their patients more often than "never/rarely" about firearm possession and storage. CONCLUSIONS: US medical students reported substantially lower rates of household gun ownership than the general population, but their participation in firearm-related counseling is also low.