Localized proton magnetic resonance spectroscopy of a cerebellar tumor in a two-year-old child

Noninvasive localized proton magnetic resonance spectroscopy (MRS) was used for differential diagnosis of a focal brain lesion in a 2.5-year-old girl. The clinical signs were a mild head tilt and neck pain. Magnetic resonance imaging (MRI) revealed a lesion in the right hemisphere of the cerebellum, but its nature remained obscure. In this lesion quantitative determinations of cerebral metabolites by fully relaxed, short-echo-time proton MRS revealed markedly lowered N-acetylaspartate (NAA) and pronounced elevations of choline-containing compounds (Cho) and myo-inositol (Ins), whereas metabolite concentrations in cortical gray matter and white matter were within normal ranges. The metabolite pattern of the lesion indicated loss of vital neuroaxonal tissue (low NAA) and enhanced glial proliferation (high Cho and Ins), which, together with the MRI morphology, suggested a brain tumor. The diagnosis was established by neurosurgical exploration and total extirpation of the tumor. Histology confirmed an astrocytoma (WHO II). After 2 weeks' recovery the child was discharged with no neurological signs.     

Left main coronary artery stenosis no longer a risk factor for early and late death after coronary artery bypass surgery--an experience covering three decades.

OBJECTIVE: To analyse early and late mortality after coronary artery bypass grafting (CABG) in patients with and without left main coronary artery (LMCA) stenosis during the 30-year period 1970-1999. METHODS: A total of 1888 of 10,647 patients (18%) who underwent a first isolated CABG at the Karolinska Hospital in Stockholm, Sweden, during 1970-1999 had significant left main coronary artery stenosis. The Swedish National Cause of Death Register was used to determine mortality up to five years after the operation. RESULTS: The proportion of patients with LMCA stenosis of all CABG patients increased from 7% during the 1970s to 26% in 1999. During 1970-1984 early mortality was 5.8% in patients with LMCA stenosis compared with 1.5% in patients without LMCA stenosis (odds ratio (OR) 3.7 (95% confidence interval (CI) 1.8-7.6)). The corresponding rates during 1995-1999 were 2.0% versus 2.2% (OR 0.8 (95% CI 0.5-1.5)), respectively. The increased risk of early death in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. Five-year survival in males was 88% after operations performed during 1994-1999 compared with 82% after CABG performed during 1970-1984. Five-year mortality, exclusive of early deaths, during 1970-1984 was higher in patients with LMCA stenosis (12.8%) than in those without (8.4%) (relative risk 1.7 (95% CI 1.1-2.5)). An increased risk of late mortality in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. CONCLUSIONS: During 1970-1999 there was a decrease of early and five-year mortality in patients with LMCA stenosis after CABG despite increase of patient age and risk factors. There were gender differences so that the risk of death in patients with compared with in those without LMCA stenosis was neutralised in males during 1985-1994 and in females during 1994-1999. The continuous decline of mortality during three decades most likely reflects improvement of the peri- and postoperative management of patients undergoing CABG during this period.     

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.     

Stereochemie substituierter Glutarsäuren, 2. Mitt. Synthese kernfluorierter,mehrfach substituierter Glutarsäuren

Stereochemistry of Substituted Glutaric Acids, II: Syntheses of Substituted 3-(4-Fluorophenyl)-glutaric Acids The stereoselective syntheses of (±)erythro- and (±) threo-3-(4-fluorophenyl)-2-methyl-glutaric acids (9), (10) by Michael addition of dimethyl malonate (2) to methyl E-2-methyl-4′-fluorocinnamate (1) via the subst. trimethylbutanetricarboxylates 3,4 and the subst. butanetricarboxylic acids 7,8 are described. 3 and 4 have been alkylated with methyl bromoacetate to the subst. tetramethylpentanetetracarboxylates 5 and 6 . Attempts towards saponification of 5 and 6 are reported.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Rapid line scan NMR angiography

This paper describes a new technique for NMR angiography based on rapid line scan projection imaging and presaturation of stationary spins. The resulting line scan angiograms are free from both misregistration artifacts common to subtraction methods and motion artifacts encountered in Fourier imaging. Moreover, line scan angiograms may be recorded within seconds and offer arbitrary fields of view as well as gradient zooming without problems due to aliasing. Three-dimensional information is obtained by rotation of the read gradient axis generating multiple view angles. Experimental line scan angiograms of the forearms of healthy volunteers have been recorded using a Bruker 2.35-T 40-cm magnet.     

Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR.

The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole).     

Proton NMR spectroscopy of cerebral metabolic alterations in infantile peroxisomal disorders.

Noninvasive studies of cerebral metabolism were performed with use of localized proton MR spectroscopy (MRS) in both healthy controls (n = 4, age 6 weeks to 2 years) and infants (n = 4, age 3-15 months) who had impaired peroxisomal functions classified as variants of Zellweger syndrome. All patients revealed a marked decrease of N-acetylaspartate in white and gray matter, thalamus, and cerebellum, indicating impairment of normal neuronal development as well as neuronal loss. In two cases an increase of cerebral glutamine and a decrease of the cytosolic polyol myo-inositol in gray matter and striatum reflected the impact of a concomitant effect on hepatic function. Two cases 3 and 6 months of age exhibited a notable elevation of mobile lipids and/or cholesterol in white matter. These patients with severe disease died within 4 weeks after the MRS examination. While an increase of free fatty acids generally associated with a lysosomal storage disease was not consistently observed by proton MRS of brain, this technique provides a convenient and safe tool for the direct assessment of neuropathologic aspects of Zellweger syndrome such as neuronal degeneration, demyelination, and consequences of compromised liver function.