Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia

Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders.     

Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety

Background

The paper presents the Motor Function Neurological Assessment (MFNU), as a tool for identifying typical motor function problems in children with Attention Deficit Hyperactivity Disorder (ADHD). The study investigated motor functions in boys diagnosed with Hyperkinetic Disorder (HKD, F.90.0). HKD corresponds to the ADHD-combined (ADHD-C) diagnosis in the DSM-IV. The paper addresses the ability of the instrument to discriminate between non-medicated boys with HKD and a control group consisting of normal non-referred boys without any clinical significant ADHD symptoms.

Methods

25 drug-naïve boys, aged 8–12 years and recently diagnosed as HKD F90.0, were compared with 27 controls, all boys in the same age range, on 17 MFNU subtests, and with a 'Total score' parameter.

Results

On the individual subtests 80–96% (median 88%) of the ADHD group showed 'moderate' to 'severe' problems, compared to 0–44% (median 14.8%) within the control group. The percentage of 'severe problems' ranged from 44–84%, (median 64%) in the ADHD group, and 0–44% (median 0%) in the control group. The highly significant differences found between the groups on all subtests, and on the Total score scores, indicated that the MFNU had a high discriminative power when children with ADHD and normal controls were compared. The Total score parameter seemed to be a meaningful discriminator of a common underlying factor of the 17 subtests used in the study.

Conclusion

The study confirms our clinical findings that the MFNU measures a consistent pattern of motor function problems in children with HKD, and that these problems are rarely represented in individuals without ADHD. Further research is needed to investigate to what extent the MFNU taps motor problems that are truly specific to ADHD, in contrast to motor problems common to children with DCD or other clinical problems.     

Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes

Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8(+) lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8(+) lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8(+) T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8(+) lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host.     

Unilateral or "side-locked" migrainous headache with autonomic symptoms linked to night guard use

Night guards are commonly prescribed as a palliative measure for bruxism, temporomandibular joint symptoms, and associated disorders. We describe a patient with a 10- to 12-year history of night guard use with concurrent unilateral side-locked migrainous headaches with autonomic symptoms characteristic of trigeminal autonomic cephalgia. These headaches were refractory to numerous pharmacological interventions. Upon self-initiated cessation of night guard use, there was complete remission of headaches. We believe the headaches were initiated by night guard-initiated irritation of the trigeminal nerve and a trigeminal autonomic reflex resulting in unilateral migrainous headache with autonomic signs.     

Clonidine as an adjuvant to intrathecal local anesthetics for surgery: systematic review of randomized trials

BACKGROUND AND OBJECTIVES: Clonidine is added to intrathecal local anesthetics to improve intraoperative analgesia and to increase the duration of sensory and motor block. The aim of this systematic review is to quantify beneficial and harmful effects of clonidine when used as an adjuvant to intrathecal local anesthetics for surgery. METHODS: We included data from 22 randomized trials (1,445 patients) testing a large variety of doses of clonidine, added to intrathecal bupivacaine, mepivacaine, prilocaine, or tetracaine. RESULTS: Clonidine 15 to 150 microg prolonged in a linear, dose-dependent manner, the time to 2 segment regression (range of means, 14 to 75 minutes) and the time to regression to L2 (range of means, 11 to 128 minutes). The time to first analgesic request (median 101 minutes, range 35 to 310) and of motor block (median 47 minutes, range 6 to 131) was prolonged without evidence of dose-responsiveness. Time to achieve complete sensory or motor block, and extent of cephalic spread remained unchanged. There were fewer episodes of intraoperative pain with clonidine (relative risk, 0.24; 95% confidence interval [CI], 0.09-0.64; number needed to treat, 13) but more episodes of arterial hypotension (relative risk, 1.81; 95% CI 1.44-2.28; number needed to harm, 8) without evidence of dose-responsiveness. The risk of bradycardia was unchanged. CONCLUSIONS: This study may serve as a rational basis to help clinicians decide whether or not to combine clonidine with an intrathecal local anesthetic for surgery. The optimal dose of clonidine, however, remains unknown.     

Subchronic racemic gamma vinyl-GABA produces weight loss in Sprague Dawley and Zucker fatty rats

Given the growing obesity epidemic, pressure to develop an effective pharmacologic treatment is mounting. Following the completion of a randomized, double-blind, placebo controlled trial as well as two small open label trials, gamma vinyl-GABA (GVG) has been shown to be safe and effective for treating cocaine and/or methamphetamine dependence. In an extension of these findings, the present study examined whether GVG could produce weight loss in adolescent as well as genetically obese animals. Specifically, adolescent Sprague Dawley and adolescent and adult Zucker fatty rats received GVG at various doses (75-300 mg/kg, i.p., racemic) for treatment periods lasting no longer than 14 consecutive days. GVG produced significant weight loss in a dose dependent fashion in all groups. These effects were marked, as average decreases of 12-20% of original body weight were observed. These findings suggest that GVG may be useful as a treatment for obesity. Further, that these results occurred in genetically obese animals offers the possibility that GVG may even help manage severe obesity resulting from binge-eating, a disorder involving food consumption in a pattern similar to the compulsive drug-seeking behavior observed in cocaine and methamphetamine dependent subjects.     

Pharmacology and signaling properties of epidermal growth factor receptor isoforms studied by bioluminescence resonance energy transfer

We have developed a new assay for measuring epidermal growth factor receptor (EGFR) activation using the bioluminescence resonance energy transfer (BRET) technology, which directly measures the recruitment of signaling proteins to activated EGFR. Our results demonstrate that EGFR BRET assays precisely measure the pharmacology and signaling properties of EGFR expressed in human embryonic kidney 293T cells. EGFR BRET assays are highly sensitive to known EGFR ligands [pEC50 of epidermal growth factor (EGF)=10.1+/-0.09], consistent with previous pharmacological methods for measuring EGFR activation. We applied EGFR BRET assays to study the characteristics of somatic EGFR mutations that were recently identified in lung cancer. In agreement with recent reports, we detected constitutively active mutant EGFR isoforms, which predominantly signal through the phosphatidylinositol-3-kinase/Akt pathway. The EGFR inhibitors Iressa or Tarceva are severalfold more potent in inhibiting constitutive activity of mutant EGFR isoforms compared with wild-type EGFR. Notable, our results reveal that most of the mutant EGFR isoforms tested were significantly impaired in their response to EGF. The highest level of constitutive activity and nearly complete loss of epidermal growth factor responsiveness was detected in isoforms that carry the activating mutation L858R and the secondary resistance mutation T790M. In summary, our study reveals that somatic mutations in EGFR quantitatively differ in pharmacology and signaling properties, which suggest the possibility of differential clinical responsiveness to treatment with EGFR inhibitors. Furthermore, we demonstrate that the EGFR BRET assays are a useful tool to study the pharmacology of ligand-induced interaction between EGFR and signaling pathway-specifying adapter proteins.     

Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases

IgA nephropathy is the most common primary glomerulonephritis and is a frequent cause for chronic kidney disease in children and young adults. Glomerular deposition of IgA also characterizes other renal disorders, including Henoch-Schoenlein purpura nephritis and immune-complex glomerulonephritis afflicting patients with liver disease due to chronic infection with the hepatitis C virus. Several treatment options are often considered, with the goal to prevent end-stage renal failure. Unfortunately, the diagnosis currently requires an invasive procedure, a renal biopsy. Because of the inherent risks, repetitive renal biopsy is frequently foregone as a means to monitor the clinical course or response to treatment. Recent advances in the analysis of the urinary proteome suggest that the excreted polypeptides include disease-specific patterns. We review recent studies of the various techniques for the identification and validation of such urinary biomarkers of IgA-associated glomerulonephritides. Currently, capillary electrophoresis coupled with mass spectrometry (MS) offers the greatest promise. To date, it seems more likely that disease-specific urinary polypeptide biomarkers are comprised of a panel of several distinct and well-defined peptides rather than a single molecule. Even most patients in clinical remission with normal clinical testing (dipstick urinalysis and quantitative proteinuria) were correctly classified by the pattern of polypeptides identified by capillary electrophoresis coupled with MS. With confirmation and refinement, such urinary testing may provide a tool for the diagnosis and monitoring of patients with IgA-associated renal diseases that is more sensitive than current standard clinical testing and far less risky than renal biopsy.     

Nephrogene systemische Fibrose

Die nephrogene systemische Fibrose ist eine progressive, potenziell tödlich verlaufende, systemische fibrosierende Erkrankung, die multiple Organe betreffen kann. Sie ist mit der Exposition von Patienten mit fortgeschrittener Niereninsuffizienz mit gadoliniumbasiertem Kontrastmittel verbunden, das bei der Magnetresonanztomographie benutzt wird. Aufgrund dieser Verbindung zwischen nephrogener systemischer Fibrose und gadoliniumhaltigen Kontrastmitteln warnte die U.S. Food and Drug Administration kürzlich vor dem Gebrauch dieser Kontrastmittel bei Patienten mit einer glomerulären Filtrationsrate unter 30 ml/min pro 1,73 m² oder mit einer akuten Nierenschädigung in Verbindung mit einem hepatorenalen Syndrom oder perioperativ bei Lebertransplantation. Lineare nicht-ionische gadoliniumbasierte Kontrastmittel, die stärker dazu neigen, Gadolinium frei zu setzen, führen häufiger zu einer nephrogenen systemischen Fibrose. Der Pathomechanismus dieser fibrosierenden Erkrankung ist noch nicht ganz verstanden, jedoch konnten Risikofaktoren identifiziert werden. Da bisher keine etablierte Therapie für die nephrogene systemische Fibrose existiert, ist die Prävention vor einer Gadoliniumexposition entscheidend für Hochrisikopatienten.