Treatment of essential tremor with the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid).

The effect of the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid; DMMDPB) on essential tremor, given in twice daily doses of 400 and 300 mg, was assessed in two brief, randomized, placebo-controlled, parallel-group, double-blinded, single-center trials in 12 and 22 patients, respectively. These trials represent the first clinical use of T2000 for a specific indication. The primary endpoint was the change in the mean scores of the treated and control groups based on the Fahn-Tolosa-Marin tremor scale. In the first study of 12 patients treated with 400 mg or placebo twice daily for 14 days, the mean change from baseline at day 14 was 19.3 (P < 0.0001) in the treated group and 9.0 (P = 0.0121) in the control group. Using a two-factor mixed ANOVA model to evaluate within group and between group changes, the effect of T2000 was significantly different from that of the placebo group (P = 0.03). In the second study of 22 patients treated with 300 mg of T2000 or placebo twice daily for 20 days, statistically significant changes were seen in treated patients compared to baseline, but the ANOVA model did not demonstrate a significant treatment effect of T2000 compared to placebo. When the treated groups from each study are compared, the 800-mg daily group is significantly different from the 600-mg daily group (P = 0.02). Some treated patients in each study, but no placebo patients, experienced marked improvement. These results support further evaluation of T2000 in the treatment of essential tremor.     

Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

EMPACT syndrome

Background: Seizure prophylaxis with phenytoin is a common measure in oncologic patients with brain metastases. In these patients, generalized severe adverse drug reactions such as erythema multiforme (EEM) may occur. However, in a subgroup of patients with brain radiation therapy, EEM‐like lesions develop particularly in the radiation field. Most recently, the acronym EMPACT ( E rythema M ultiforme associated with P henytoin A nd C ranial radiation T herapy) was proposed to specifically describe this syndrome. Patient/Method: Here, we report on EMPACT syndrome in a 46‐year‐old woman. Therapeutic measures included seizure prophylaxis with phenytoin and total brain radiation therapy of brain metastases from bronchial carcinoma. Three weeks after introduction of phenytoin, the patient presented with EEM‐like skin lesions restricted to the original radiation field and facial mucocutaneous involvement. After a few days, the rash spread to the upper part of the body. She was also in poor general condition. Results: The immediate cessation of phenytoin therapy, combined with administration of systemic corticosteroids and high dose immunoglobulins along with intensive local treatment and pain medications, resulted in complete resolution of the skin eruption. Patch testing to phenytoin was positive after 72 hours. Conclusion: EMPACT should be classified as an specific entity among the EEM‐like drug reactions as it only appears after radiotherapy and seizure prophylaxis with the anticonvulsant phenytoin. We propose including specific type IV‐sensitization to phenytoin into the definition of EMPACT.     

Electrodynamics and ultimate SNR in parallel MR imaging.

The purpose of this article is to elucidate inherent limitations to the performance of parallel MRI. The study focuses on the ultimate signal-to-noise ratio (SNR), which refers to the maximum SNR permitted by the electrodynamics of the signal detection process. Using a spherical model object, it is shown that the behavior of the ultimate SNR imposes distinct limits on the acceleration rate in parallel imaging. For low and moderate acceleration, the ultimate SNR performance is nearly optimal, with geometry factors close to 1. However, for high reduction factors beyond a critical value, the ultimate performance deteriorates rapidly, corresponding to exponential growth of the geometry factor. The transition from optimal to deteriorating performance depends on the electrodynamic characteristics of the detected RF fields. In the near-field regime, i.e., for low B0 and small object size, the critical reduction factor is constant and approximately equal to four for 1D acceleration in the sphere. In the far-field wave regime the critical reduction factor is larger and increases both with B0 and object size. Therefore, it is concluded that parallel techniques hold particular promise for human MR imaging at very high field.     

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.     

High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging.

An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution=234 x 468 microm2) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the study of small rodents at high fields.     

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

大肠杆菌内毒素所致肺血管收缩部位及山莨菪碱的作用

将动、静脉阻断法用于恒速灌流的在体山羊左肺,使其总压力降区分为动脉端、静脉端及中间段三部分。大肠杆菌内毒素主要升高肺静脉端压力降及肺毛细血管压;山莨菪碱可显著缓解内毒素所致的改变,但对正常肺血管各段压力降无明显影响。5-羟色胺主要升高肺动脉端压力降,对肺静脉端及毛细血管压无明显影响。去甲肾上腺素及组胺主要升高肺静脉端压力降及肺毛细血管压,但对肺动脉端无明显影响。去甲肾上腺素和组胺可能介导内毒素性肺动脉高压。     

Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.