Volker Diehl, 60 Jahre

Ohne Zusammenfassung     

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.     

New Biological and Clinical Roles for the n–6 and n–3 Fatty Acids

Four new findings of the biochemistry and biology of the essential n–6 and n–3 fatty acids have recently been demonstrated. These findings will augment current knowledge as to the role of the essential fatty acids in human health.     

Quantifying the intra- and extravascular contributions to spin-echo fMRI at 3 T.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.     

Potential role of flavonoids in the prevention of intestinal neoplasia

Intestinal neoplasia (adenomas and carcinomas) can possibly be prevented by a diet rich in vegetables and fruits, treatment with aspirin and other nonsteroidal antiinflammatory drugs, and early colonoscopic removal of adenomas. Ballast, fiber, and secondary plant products could play a major role in colon cancer prevention. Recently there has been much experimental work in vitro and in vivo about flavonoids as inducers of bioprevention. Flavonoids are secondary plant products with a wide variety of beneficial biological properties, and they possess anticarcinogenic, antimutagenic, and antioxidative modes of actions. Flavonoids are the main components of a healthy diet containing fruits and vegetables and are concentrated especially in tea, apples, and onions. We will focus this review on flavonoids which are derived from tea products such as proanthocyanidins (green tea) and flavons (camomille tea). Oral supplementation with bioflavonoids derived from tea could be used in humans to prevent growth of intestinal neoplasia such as adenomatous polyps of the colon. Flavonoids are a large group of natural compounds of which only a few have been used in animal models, cell cultures, and enzyme studies to inhibit mutagenic and carcinogenic events. Their clinical mode of action was evaluated by epidemiological studies, but no intervention studies in humans have been performed so far. In vitro flavonoids can bind electrophils, inactivate oxygen radicals, prevent lipid peroxidation, and inhibit DNA oxidation. In cell cultures they increase the rate of apoptosis, inhibit cell proliferation, and angiogenesis. In vivo they can induce the activities of protective enzymes (conjugating enzymes such as glutathione transferases and glucuronosyl transferases) of the intestine and the liver. In models of intestinal polyposis, flavonoids suppress polyp formation. Some epidemiological studies show a protective effect of flavonoids contained in fruits, vegetables, and tea.Flavonoid mixtures of tea origin supplied as nutritional supplements could be studied as a new way of bioprevention of intestinal neoplasia (colon adenomas and cancer). Therefore, a controlled, randomized clinical study should be performed to evaluate the efficacy of flavonoids.     

Need for bilateral arthroplasty for coxarthrosis 1, 477 replacements in 1, 199 patients followed for 0-14 years

During the 10-year period 1981-1990, 1, 199 patients in the county of South Jutland, Denmark, had 1, 477 primary total hip arthroplasties (THA) performed because of primary arthrosis (OA).

The patients were followed until the end of 1994, with a mean follow-up of 5.6 (0-14) years. Bilateral operations were performed on 356 patients, whereas 248 patients had died with only 1 THA.

The cumulated risk of replacement of the contralateral hip was approximately 0.15 1 year after replacement of the first hip, 0.20 after 2 years, 0.29 after 5 years and 0.47 after 10 years, respectively.

During the follow-up period, the demand for a THA of the contralateral hip continued to be approximately 15 times higher than in the general population.     

"Chronic painter''s syndrome". A reanalysis of psychological test data in a group of diagnosed cases, based on comparisons with matched controls

Twenty solvent-exposed workers, most of them painters, had been diagnosed as cases of toxic encephalopathy in 1978/79. Two years later they were re-examined with an extensive battery of neuropsychological tests. Their performance was unchanged on retesting. We have now compared their test results with those of non-exposed control subjects. Previous impressions of significant intellectual impairment in the solvent-exposed patients could not be confirmed when the influence of age, education, and intelligence was taken into consideration. The present group with presumed toxic encephalopathy is assumed to be representative of other patients who were similarly diagnosed in our department. The presently reanalyzed cases had been diagnosed as brain damaged and reported as such in the literature. Thus, they may have contributed to the formation of the concept of the "chronic painters' syndrome" with dementia.     

Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary–adrenal axis

Synthetic glucocorticoids are administered to pregnant women in premature labour to accelerate fetal lung maturation at a time when fetal cerebrovascular and endocrine systems are maturing. Exposure to glucocorticoids at 0.8–0.9 of gestation increases peripheral and cerebrovascular resistance (CVR) in fetal sheep. We examined whether the increase of CVR and its adverse effect on cerebral blood flow (CBF) depend on the current level of maturation of the pituitary–adrenal axis and the cerebrovascular system. Using fluorescent microspheres, regional CBF was measured in 11 brain regions before and 24 h and 48 h after the start of 3.3 μg kg⁻¹ h⁻¹ betamethasone ( n = 8) or vehicle ( n = 7) infusions to fetal sheep at 0.73 of gestation. Hypercapnic challenges were performed before and 24 h after the onset of betamethasone exposure to examine betamethasone effects on cerebrovascular reactivity. Betamethasone exposure decreased CBF by approximately 40% in all brain regions after 24 h of infusion ( P < 0.05). The decline in CBF was mediated by a CVR increase of 111 ± 16% in the cerebral cortex and 129 ± 29% in subcortical regions ( P < 0.05). Hypercapnic cerebral vasodilatation and associated increase in CBF were blunted ( P < 0.05). Fetal CBF recovered after 48 h of betamethasone administration. There were no differences in glucocorticoid induced CBF and CVR changes compared with our previous findings at 0.87 of gestation. We conclude that the cerebrovascular effects of antenatal glucocorticoids are independent of cerebrovascular maturation and preparturient increase in activity of the fetal pituitary–adrenal axis.