Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Cytologic findings in stage I adenocarcinoma of the lung: Implications for the detection of early lung cancer

Preoperative cytologic examinations were performed on bronchial material from 92 patients with postsurgical (pathologic) stage I (American Joint Committee) adenocarcinoma of the lung. All patients were followed up for at least 5 years or until death; thus, cases of adenocarcinoma metastatic to the lungs were virtually excluded. Only 22 patients (24%) had abnormal preoperative cytologic findings. This low cytologic sensitivity is ascribed to the small size and peripheral location of the tumors. Large lesions of high histologic grades were more likely to have positive preoperative cytologic findings than small, well-differentiated ones.     

Dissociation of Depletional Induction and Posttransplant Lymphoproliferative Disease in Kidney Recipients Treated With Alemtuzumab

Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.     

Minimal instructions improve the performance of laypersons in the use of semiautomatic and automatic external defibrillators

Introduction  

There is evidence that use of automated external defibrillators (AEDs) by laypersons improves rates of survival from cardiac arrest, but there is no consensus on the optimal content and duration of training for this purpose. In this study we examined the use of semiautomatic or automatic AEDs by laypersons who had received no training (intuitive use) and the effects of minimal general theoretical instructions on their performance.     

Automated CTA quantification of internal carotid artery stenosis: a pilot trial.

PURPOSE: To evaluate the feasibility and accuracy of automated analysis software for use with multidetector computed tomographic angiography (CTA) in the exact grading of internal carotid artery stenosis. METHODS: A retrospective pilot trial was performed using CTA datasets from 87 stenotic carotid arteries in 46 consecutive patients (34 men; median age 73.5 years) with known cerebrovascular disease. Internal carotid artery (ICA) stenosis was graded according to NASCET criteria by 2 experienced vascular radiologists in consensus using axial source images as well as curved planar reformations and digital subtraction angiography (DSA). These results were then compared to those obtained from the automated CTA analysis software and the results of manually adapted automated CTA analysis. RESULTS: Measurements from automated CTA analysis as well as manually adapted automated CTA analysis correlated significantly to those of axial/reformatted CTA and DSA (r=0.53 and r=0.82, r=0.58 and 0.70, respectively, all p<0.05). Compared to axial/reformatted CTA measurements, automated CTA analysis had a median difference of -16%, while manually adapted automated CTA had a difference of -10%. Corresponding differences in a comparison with DSA were +4% and -2%, respectively. Circumferential calcification or kinking of the ICA origin did not significantly interfere with these differences (all p>0.05). Sensitivities for the detection of ICA stenosis >70% by manually adapted automated CTA analysis and automated measurement were 44.2% and 34.9%, respectively, versus axial/reformatted CTA. Compared with DSA as the gold standard, the sensitivities were 54.2% and 62.5%, respectively. Specificities for both methods and gold standards all exceeded 90%. CONCLUSION: Commercially available automated CTA analysis is a feasible tool, but sensitivities are still not sufficient for clinical application.     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

Prevalence of traumatic injuries to the permanent incisors in candidates for orthodontic treatment

Abstract  – The dental records made on presentation of 1367 consecutive patients (731 females and 636 males) for orthodontic treatment at a private orthodontic practice between 1998 and 2002 were examined for data relating to trauma to the permanent incisors. The results showed that 10.3% of these patients had suffered from dental trauma before the onset of orthodontic treatment. The highest prevalence of dental trauma was determined in the 11–15 years age group, corresponding to the dental developmental stage of the late mixed dentition. The most frequently affected teeth were the maxillary central incisors (79.6%), and the most common types of trauma were fracture of enamel–dentin without pulpal involvement (42.7%) and fracture of enamel (33.8%). Compared to patients with normal overjet and adequate lip coverage, the frequency of dental trauma was significantly higher in patients with increased overjet and adequate lip coverage ( P  = 0.028) or with increased overjet and inadequate lip coverage ( P  = 0.003). The results of the present study indicate that a significant percentage of candidates for orthodontic treatment, and especially those with increased overjet and inadequate lip coverage, suffer trauma to their permanent incisors before the onset of orthodontic treatment. It might also be concluded that preventive orthodontic treatment of such patients should be initiated and completed before the age of 11, i.e. in the early to middle mixed dentition.