Diagnosis of perimesencephalic nonaneurysmal subarachnoid hemorrhage with computed tomography

Objective: In 4% to 31% of patients with acute subarachnoid hemorrhage (SAH), no underlying cause is identified. Blood is restricted to the perimesencephalic cisterns in about two thirds of these patients. These patients are identified as having perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH), a syndrome based on the interpretation of computed tomography (CT) findings on admission, with an excellent prognosis, far better than other patients with SAH with or without an aneurysm. However, the diagnosis is subject to interrater variability, and differentiation between PNSAH and ruptured supratentorial aneurysm by means of CT has not been investigated. Therefore we investigated the validity of prediction of PNSAH with CT scan. Methods: A total of 303 consecutive patients, admitted within 72 hours after the initial bleeding with symptoms and signs of spontaneous SAH, which was confirmed by CT or spectrophotometric analysis of the cerebrospinal fluid (CSF) in whom either a selective 4-vessel angiogram (n = 293) or postmortem examination (n = 10) was performed, were studied. Results: We found an interrater agreement for the diagnosis perimesencephalic nonaneurysmal subarachnoid hemorrhage of 93% and a κ value of 0.65. Sensitivity was 30% for observer 1 and 46% for observer 2. The positive predictive value was 73% for observer 1 and 76% for observer 2. Among those diagnosed as having PNSAH, we found vertebrobasilar artery aneurysms in 19% (both raters) and internal carotid artery aneurysms in 5% (observer 1) and 8% (observer 2). Conclusion: We conclude that PNSAH can be distinguished on CT in the majority of patients; however, the angiographical management in PNSAH should not differ from other SAHs.     

Effects of corticosterone and the β-agonist isoproterenol on glutamate receptor-mediated synaptic currents in the rat basolateral amygdala

Behavioral and field potential studies suggest that – shortly after stress – noradrenaline and corticosterone interact to affect the function of basolateral amygdala (BLA) neurons. Here, we tested, at the single-cell level, to what extent α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated and N -methyl- d -aspartate (NMDA) receptor-mediated synaptic responses of identified BLA neurons are affected by relatively low concentrations of the β-agonist isoproterenol, how this is influenced by concomitant application of corticosterone, and how isoproterenol effects are influenced by corticosterone given several hours in advance. We observed that isoproterenol concentration-dependently enhances AMPA receptor-mediated (but not NMDA receptor-mediated) responses; near-maximal effects were induced by 1 μ m isoproterenol. Corticosterone alone did not rapidly affect AMPA and NMDA-mediated responses. NMDA-mediated responses were also not affected by the hormone in a delayed manner; AMPA-mediated responses were slowly suppressed by corticosterone, but only with high stimulation intensities. If corticosterone was co-applied with isoproterenol (0.4 or 1 μ m ), facilitation of AMPA-mediated responses was comparable to that seen with isoproterenol alone. However, if corticosterone was applied several hours in advance of the β-agonist, the effect of 0.4 μ m isoproterenol on AMPA-mediated responses was reduced. This supports the notion that, in the BLA, isoproterenol facilitates synaptic transmission, a process that can be suppressed by corticosterone in a slow manner. Overall, the data suggest that, despite the previously reported ability of corticosterone to cause long-term increases in excitability in the BLA, the hormone still retains some capacity to slowly exert a normalizing action on local activity.     

A hierarchical model for the relationships between general and specific vulnerability factors and symptom levels of generalized anxiety disorder

The present study examined a hierarchical model for the relationships between general and specific vulnerability factors and symptom manifestations of generalized anxiety disorder (GAD). A clinical sample of patients with GAD (N = 137) completed a set of self-report questionnaires for measuring neuroticism, extraversion, intolerance of uncertainty, metacognitive beliefs, and symptoms of generalized anxiety (i.e., worry) and depression. A bootstrapping analysis yielded support for a model in which the relation between the general vulnerability factor of neuroticism and symptoms of GAD were mediated by the specific vulnerability factors of intolerance of uncertainty and negative metacognitions. Implications for the classification and treatment of GAD are discussed.     

Effectiveness of an Outreach Treatment Program for Inner City Crack Abusers: Compliance,Outcome, and Client Satisfaction

In a randomized controlled trial the effectiveness of an outreach treatment program (OTP) was compared with standard addiction care services for hard-drug addicts in Rotterdam (The Netherlands). The study aimed at chronic, high-risk crack abusers who were insufficiently engaged in standard addiction treatment services. Data were collected from February 2000 to December 2001. A total of 124 subjects participated in the study at baseline. Follow-up data were available for 94 subjects. Outcome measures included treatment compliance, outcome, and satisfaction. Data were collected by means of monthly registrations, EuropAsi interviews and an evaluation form. There was a high compliance with OTP in the treatment group; the average length-of-stay was 6 months, with visits three times a week. Although both groups were well represented in standard care, participation was mainly based on methadone maintenance. Subjects treated in OTP showed significant improvements in physical health, general living conditions, and psychiatric status, but no change in employment, substance abuse, and legal status. The control group remained almost unchanged. Clients of OTP reported feeling very satisfied with their treatment. On-the-spot incentives and a positive relationship with the care provider were directly associated with treatment retention. An outreach treatment program, as conducted in this study, is associated with high compliance, general improvement, and treatment satisfaction. Characteristics of this treatment modality are (1) assertive outreach, (2) a mixed program with incentives, and (3) a strong focus on individual-bound therapy. Further research is needed with larger groups and similar conditions at baseline assessment.     

MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: A pilot study

We developed a new method for immobilization of the fix lower extremities by using a thermoplastic mask, a carbon fiber base plate, a customized headrest, and an adjustable angle holder. The lower extremities of 11 patients with lower extremity tumors were immobilized by this method. CT simulation was performed for each patient. For all 11 patients, the device fit was suitable and comfortable and had good reproducibility, which was proven in daily radiotherapy.     

Stress-induced dilated cardiomyopathy in a knock-in mouse model mimicking human titin-based disease

Mutations in a variety of myofibrillar genes cause dilated cardiomyopathy (DCM) in humans, usually with dominant inheritance and incomplete penetrance. Here, we sought to clarify the functional effects of the previously identified DCM-causing TTN 2-bp insertion mutation (c.43628insAT) and generated a titin knock-in mouse model mimicking the c.43628insAT allele. Mutant embryos homozygous for the Ttn knock-in mutation developed defects in sarcomere formation and consequently died before E9.5. Heterozygous mice were viable and demonstrated normal cardiac morphology, function and muscle mechanics. mRNA and protein expression studies on heterozygous hearts demonstrated elevated wild-type titin mRNA under resting conditions, suggesting that up-regulation of the wild-type titin allele compensates for the unstable mutated titin under these conditions. When chronically exposed to angiotensin II or isoproterenol, heterozygous mice developed marked left ventricular dilatation (p  < 0.05) with impaired fractional shortening (p  < 0.001) and diffuse myocardial fibrosis (11.95 ± 2.8% vs. 3.7 ± 1.1%). Thus, this model mimics typical features of human dilated cardiomyopathy and may further our understanding of how titin mutations perturb cardiac function and remodel the heart.