Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury

BACKGROUND: Patients with Parkinson disease characteristically exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography, a new neuroimaging technique. The same echo feature of the SN can be identified in 9% of healthy adults. OBJECTIVE: To evaluate the relevance of the echogenic SN in healthy adults. DESIGN: In the first part of the study, 10 healthy subjects younger than 40 years with a distinct SN hyperechogenicity underwent extensive neurological, motor, neuropsychological, and fluorine 18-dopa positron emission tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10 subjects with a low echogenic SN. In the second part of the study, the postmortem brains of 20 patients without extrapyramidal disorders during their lifetime were sonographically examined with a particular focus on SN echogenicity. Subsequently, one half of the brain was prepared for heavy metal analysis, the other for a histological examination. RESULTS: Healthy subjects with SN hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake, especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right side, P =.009), whereas their neuropsychological and motor performance were normal. Postmortem studies showed that the echogenicity of the SN correlated with its iron content. CONCLUSIONS: Increased echogenicity of the SN, characteristically seen in Parkinson disease, is related to a functional impairment of the nigrostriatal system (even in young healthy adults) that can be revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related to a higher tissue iron level, which is known to enhance the cells' generation of reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography may identify a susceptibility marker for the development of nigral injury that can be detected early in life, prior to the onset of Parkinson disease.     

Selective suppression of hippocampal region hyperexcitability related to seizure susceptibility in epileptic El mice by the GABA-transporter inhibitor tiagabine

High seizure susceptibility in El mice is associated with disinhibition in the dentate gyrus (DG) and paired-pulse facilitation in the CA3 area in hippocampal slices [Brain Res. 745 (1997) 165; Brain Res. 779 (1998) 324]. A decrease in gamma-aminobutyric acid (GABA)-mediated inhibition and an increase in excitatory inputs to the major neurons seem to be the responsible mechanisms, respectively, for these phenomena. In this study, we examined the effects of tiagabine, an inhibitor of GABA transporter, on hyperexcitation in vivo and in slice preparations. Tiagabine (0.3-0.5 mg/kg) suppressed the occurrence of seizures to about 20% of controls with an ED(50) value of about 0.17 mg/kg. In addition, perfusion of hippocampal slices with tiagabine (20 microM) counteracted the paired-pulse facilitation in the CA3 region over the entire range of interpulse intervals (P<0.05, two-way ANOVA) and reduced the disinhibition in the DG measured at 10 and 20 ms during short interpulse intervals (P<0.005, paired t-test). The CA1 region in the El mice, as well as in a non-epileptic parental strain of ddY mice did not respond to the drug. However, frequency potentiation of CA3 was enhanced in both strains (P<0.05, paired t-test). Our results suggest that within the hippocampus the antiepileptic action of tiagabine is selectively suppressive for hyperexcitability of DG and CA3, which are responsible for seizure-susceptibility in El mice.     

Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein

Isopentenyl diphosphate and dimethylallyl diphosphate serve as the universal precursors for the biosynthesis of terpenes. Although their biosynthesis by means of mevalonate has been studied in detail, a second biosynthetic pathway for their formation by means of 1-deoxy-D-xylulose 5-phosphate has been discovered only recently in plants and certain eubacteria. Earlier in vivo experiments with recombinant Escherichia coli strains showed that exogenous 1-deoxy-D-xylulose can be converted into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate by the consecutive action of enzymes specified by the xylB and ispCDEFG genes. This article describes the transformation of exogenous [U-(13)C(5)]1-deoxy-D-xylulose into a 5:1 mixture of [U-(13)C(5)]isopentenyl diphosphate and [U-(13)C(5)]dimethylallyl diphosphate by an E. coli strain engineered for the expression of the ispH (lytB) gene in addition to recombinant xylB and ispCDEFG genes.     

Tissue engineering of an auto-xenograft pulmonary heart valve

To improve the durability of stentless valves without losing their excellent hemodynamic function, a new-generation auto-xenograft was developed and evaluated. A piece of vein was harvested from 3 juvenile sheep 6 weeks before implantation of the valve. Endothelial cells from the vein material were cultivated and used to reendothelialize a decellularized porcine pulmonary valve. The tissue-engineered valve was implanted into the right ventricular outflow tract of the juvenile sheep. It was explanted after 100 days and assessed macroscopically as well as by x-ray, light microscopy (hematoxylin and eosin staining and von Kossa staining), and scanning electron microscopy. Calcium content of the cusps was determined quantitatively by atomic absorption spectrometry. The sheep implanted with the valve recovered quickly without any problems during the observation period. X-ray examination of the 3 explanted valves showed no cusp calcification, which was confirmed by histological study. Atomic absorption spectrometry showed low tissue calcium content. A clinical safety and feasibility trial with an allograft valve prepared the same way showed excellent short-term results in 6 patients.     

Inflammatory response to stent implantation: differences in femoropopliteal,iliac, and carotid arteries

PURPOSE: To examine how frequently Breast Imaging Reporting and Data System (BI-RADS) mammographic screening assessments were associated with expected clinical management recommendations. MATERIALS AND METHODS: Seven Breast Cancer Surveillance Consortium mammography registries recorded screening assessments and recommendations in 1997 to identify the proportion of women in each BI-RADS category. The first screening assessment for a woman without cancer or a prior mammogram within 9 months was associated with its independently recorded recommendation. RESULTS: Among 292,795 women, screening assessments included 269,022 (91.9%) with a "negative" or "benign finding," and 267,103 (99.3%) of these women were recommended for normal interval follow-up. Among 11,861 (4.1%) women with screening assessments of "probably benign finding," 4,782 (40.3%) were recommended for short interval follow-up as expected on the basis of the BI-RADS, but a high proportion (36.9%) were recommended for additional imaging. Among 1,625 (0.6%) women with "suspicious abnormality," most were recommended for biopsy (48.7%) or clinical examination and/or surgical consult (9.0%), but many were recommended for additional imaging (38.7%). Among 243 (0.1%) women with screening assessments "highly suggestive of malignancy," a majority were recommended for biopsy (73.3%) or clinical examination and/or surgical consult (18.1%) consistent with BI-RADS, but some were recommended for additional imaging (6.6%). CONCLUSION: BI-RADS assessments and management recommendations are consistent for negative and benign assessments, but inconsistencies were found in assessments and recommendations for mammographic abnormalities.     

Steady-state free precession projection MRI as a potential alternative to the conventional chest X-ray in pediatric patients with suspected pneumonia

Magnetic resonance imaging of the lung tissue is thought to be hardly possible due to physical limitations especially the low proton density, susceptibility, and motion artifacts. The objective of our study was to evaluate and refine a very fast MR technique at a low field strength which overcomes the limitations in MR lung imaging. Thirty-five investigations were performed in 30 pediatric patients with suspected pneumonia. The MR investigations were performed in coronal slice orientation without cardiac or respiratory triggering in a low-field MR system. An optimized true fast imaging with steady precession sequence was applied. The MR images and the corresponding conventional chest radiographs were evaluated. The examination time per slice was 1.6 s. No motion artifacts could be observed. The signal-to-noise ratio for pulmonary parenchyma ranged from 4.9 to 7.1. All pathological findings of the chest X-ray images were correctly identified by the MRI (κ=0.82–0.85). Effusions as well as small pneumonic infiltrates were more precisely detected by the MRI investigation (κ=0.82) as compared with X-ray. Low-field projection MRI is a promising alternative to pediatric chest X-ray. Due to its short examination time, it overcomes the physical limits of usual MRI methods and provides comparable diagnostic information. Electronic Publication     

A method of scaling the 3D electron pencil-beam dose calculation to obtain accurate monitor units for irregularly-shaped electron beams.

A method for determining monitor units (MU) for electron beams using a 3D pencil beam dose algorithm is described. A set of correction factors (OF(c)) to the pencil beam dose is generated that transforms the output into dose per MU. The OF(c)s depend on cone selection, field size, and source-to-surface distance (SSD) for a given electron energy. The dose per MU is determined by scaling the dose by the OF(c). The OF(c) value is determined using a measured set of relative output factors (OF(rel)) for various field sizes and SSD. The pencil-beam algorithm is used to compute the "raw" value (OF(p)) to each of the OF(rel) measurement points. The OF(c) is the ratio of the measured OF(rel) to the calculated OF(p). The OF(c) value for irregularly-shaped electron fields or for electron fields at extended SSD may be interpolated from the OF(c) table. The interpolation over SSD is performed linearly using the central axis SSD. The interpolation over field size is more complicated and uses the minimum area-circumscribing rectangle around the field shape. Due to the relative flatness of the OF(c), the interpolation is less error prone than the more common direct interpolation of the output factors. Computations were performed in the ADAC Pinnacle3 Planning System. Measurements were obtained using a Varian 2300c for 6 and 15 MeV. The results show that this method can predict the dose per MU within 1% to 2% for clinical fields and within 3% to 4% for extreme field shapes.     

Diagnosis and staging of pancreatic cancer: comparison of mangafodipir trisodium-enhanced MR imaging and contrast-enhanced helical hydro-CT

OBJECTIVE: The purpose of this study was to compare mangafodipir trisodium-enhanced MR imaging performed with a phased array coil and contrast-enhanced single-detector helical CT for accuracy in the detection and local staging of pancreatic adenocarcinoma and in the differentiation between cancer and focal pancreatitis. SUBJECTS AND METHODS: Forty-two patients with suspected pancreatic masses underwent contrast-enhanced helical CT and mangafodipir trisodium-enhanced MR imaging at 1.5 T. The images were assessed for the presence or absence of tumors; characterization of masses; and presence of vascular invasion, lymph node metastases, or liver metastases. Imaging findings were correlated with findings at laparotomy, laparoscopy, biopsy, or follow-up. RESULTS: Focal masses were present in 36 patients (cancer, n = 26; focal pancreatitis, n = 7; other, n = 3). The sensitivity for lesion detection of MR imaging was 100% and of CT, 94%. Two small malignant lesions were missed on CT. For the diagnosis of tumor nonresectability, the sensitivity of MR imaging and CT was 90% and 80%, respectively. Liver metastases were missed on MR imaging in one of the eight patients and on CT in four. For differentiation between adenocarcinoma and nonadenocarcinoma, the sensitivity of MR imaging was 100% (positive predictive value, 90%; negative predictive value, 100%), and the sensitivity of CT was 92% (positive predictive value, 80%; negative predictive value, 67%). Receiver operating characteristic analysis revealed that the mean area under the curve for MR imaging was 0.920 and for CT, 0.832 (not significant). CONCLUSION: Mangafodipir trisodium-enhanced MR imaging is as accurate as contrast-enhanced helical CT for the detection and staging of pancreatic cancer but offers improved detection of small pancreatic metastases and of liver metastases compared with CT.