Trends of research and practice in "occupational risk prevention" as seen in Germany

Hypothesis and scenarios of future developments in ORP and ORP research are derived. Based on an analysis of events in the past, on the content and process of research projects in the German "humanization" program, on literature analysis and expert interviews 19 anamnesis to diagnosis relationships are formulated concentrating on the following topics: 1. Innovation potentials and value systems of ORP research, 2. Fields and topics of ORP research of the future, 3. Service-oriented systems of actors in ORP, 4. Demands and limits for research transfer. So the creative potential of the ORP community in Germany was used to conclude on recommendations for ORP developments.     

High dietary iron concentrations enhance the formation of cholesterol oxidation products in the liver of adult rats fed salmon oil with minimal effects on antioxidant status

The aim of this study was to investigate the effect of high dietary iron concentrations on the antioxidant status of rats fed two different types of fat. Four groups of male adult Sprague-Dawley rats were fed diets with adequate (50 mg iron supplemented per kg diet) or high (500 mg iron supplemented per kg diet) iron concentrations with either lard or salmon oil as dietary fat at 100 g/kg for 12 wk. The antioxidant status of the rats was profoundly influenced by the type of fat. Rats fed salmon oil diets had higher concentrations of thiobarbituric acid-reactive substances (TBARS) (P < 0.001), various cholesterol oxidation products (COP) (P < 0.001), total and oxidized glutathione (P < 0.05) and a lower concentration of alpha-tocopherol (P < 0.05) in liver and plasma than rats fed lard diets. The iron concentration of the diet did not influence the concentrations of TBARS, the activities of superoxide dismutase and glutathione peroxidase or the concentration of alpha-tocopherol in plasma or liver. The activity of catalase (P < 0.01) and the concentrations of total, oxidized and reduced glutathione (P < 0.05) in liver were slightly but significantly higher in rats fed high iron diets than in rats fed adequate iron diets, irrespective of the dietary fat. Rats fed the high iron diets with salmon oil, moreover, had higher concentrations of various COP in the liver (P < 0.001) than rats fed adequate iron diets with salmon oil. These results suggest that feeding a high iron diet does not generally affect the antioxidant status of rats but enhances the formation of COP, particularly if the diet is rich in polyunsaturated fatty acids.     

Nasal function in self-reported chemically intolerant individuals

Nasal function has not yet been investigated under controlled exposures in individuals with self-reported Multiple Chemical Sensitivity (sMCS). Therefore, anterior rhinomanometry and acoustic rhinometry were applied in 12 individuals with sMCS, and 12 age-matched controls. The sMCS individuals and controls were selected on the basis of a standardized questionnaire. Controlled 4-hr exposures to ethylbenzene and 2-butanone were performed during 4 sessions. Exposures were close to the current German threshold limit values, and they approximated odor thresholds. Subjects with sMCS had a significant decrease in the flow value in anterior rhinomanometry, independent of substance and doses, compared with controls. This result suggests somatic reactions to the exposure. The result must be confirmed in additional studies, and pathophysiological examinations must be performed. For these investigations, anterior rhinomanometry was usable, but acoustic rhinometry can be recommended only after sufficient standardization has occurred. Furthermore, biochemical parameters of nasal mucosa must be considered.     

Postvaccinal inflammatory neuropathy: peripheral nerve biopsy in 3 cases

Autoimmune inflammatory polyneuropathy (PN) can be triggered by vaccination. We report 3 such cases. A 36-year-old female nurse presented 15 days after a hepatitis B vaccination (HBV) with acute sensory disturbances in the lower limbs. She had severe ataxia but no weakness. Cerebrospinal fluid (CSF) protein level was 84 mg/100 mL, with 3 lymphocytes. A 66-year-old man presented 21 days after HBV with severe motor and sensory PN involving all 4 limbs. A 66-year-old man presented 15 days after a yellow fever vaccination with progressive motor and sensory PN involving all 4 limbs and bilateral facial paralysis. CSF protein level was 300 mg/100 mL, with 5 lymphocytes. Six weeks later, a tracheostomy was performed. In these 3 patients, the nerve deficits lasted for months. In each case, peripheral nerve biopsy showed KP1-positive histiocytes but no T-lymphocytes in the endoneurium. On ultrastructural examination, there was axonal degeneration in the first 2 cases; in case 2, a few myelinated fibers exhibited an intra-axonal macrophage but the myelin sheath was preserved. There was only 1 example of macrophage-associated demyelination in case 2, but these were numerous in case 3. It is likely that in the first 2 cases, an autoimmune reaction against some axonal or neuronal components was triggered by HBV. It induced an acute sensory ataxic PN in case 1 and an acute motor and sensory axonal neuropathy (AMSAN) in case 2. The third patient had a chronic inflammatory demyelinating PN, likely triggered by yellow fever vaccination.     

Developments in antipsychotic therapy with regard to hypotheses for schizophrenia

The typical antipsychotic drugs like chlorpromazine and haloperidol were discovered by serendipity in the 1950s. A number of so-called "me too" drugs with similar chemical structures and modes of action were marketed in the subsequent years. The first atypical antipsychotic, clozapine, was an exception because it lacked some of the pharmacological properties of the typical antipsychotics related to the extrapyrimidal motor system. This unique feature of clozapine significantly broadened understanding of the mode of action of antipsychotics, and created new hypotheses for schizophrenia. Hypothesis-orientated development of new drugs was only recently initiated. Abnormalities of the immune system in schizophrenia are being increasingly discussed: shifts in the levels of T helper cells subsets 1 and 2 (Th1 and Th2) have been observed, and studies with risperidone and the cyclooxengenase (COX2) inhibitor celecoxib as an add-on therapy have provided very promising results. The glutamate N-methyl-D-aspartate (NMDA) receptors have also been investigated in relation to neuropathological abnormalities in prefrontal areas of the brain of patients with schizophrenia. This may lead to new technologies like artificial networks related to the glutamate NMDA receptor system. New molecular biological techniques used in pharmacogenomics and proteomics offer new and exciting directions for future drug developments.     

X-ray digital subtraction angiography with 1 mol/L gadobutrol: results from a comparative porcine study With iodinated contrast agents

RATIONALE AND OBJECTIVES: To evaluate prospectively diagnostic accuracy of 1 mol/L gadobutrol as a contrast agent for intraarterial x-ray digital subtraction angiography (DSA) in comparison to iodinated, nonionic contrast media and 0.5 mol/L gadolinium-DTPA. METHODS: Flush arteriograms (ascending, descending, abdominal aorta, iliac, and femoral arteries) and selective angiograms (carotid, renal, and visceral arteries) were obtained from bilateral femoral arterial access (5 F sheaths) in 10 domestic pigs (70 kg body weight). Digital subtracted angiograms were obtained during injection of undiluted 1 mol/L gadobutrol, 300 mg I/mL iopromide, or 0.5 mol/L gadopentetate. Injection parameters (volume and velocity) were similar for all three contrast agents. In paired arteries, two different contrast media were used during the same angiographic run. Diagnostic quality and accuracy of the angiograms were evaluated on a three-step scale by three independent blinded investigators. RESULTS: Sufficient nonselective angiographic images were obtained in 90% of cases using iodinated contrast material. Gadobutrol achieved sufficient nonselective angiograms in 64%. Selective angiograms were sufficient in 98% using iodinated contrast material, 90% using 1 mol/L Gadobutrol and 48% using 0.5 mol/L Gd-DTPA. Adverse reactions to any of the used contrast agents were not noted. CONCLUSION: One mol/L Gadobutrol solution allows x-ray digital subtraction angiography with a diagnostic accuracy equivalent to 300 mg/mL iodinated contrast media, if selective injections are performed. Flush aortograms are of inferior image quality to iodinated contrast material.     

A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy

This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 [0.67] grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation. Received: 6 August 2001, Received in revised form: 6 March 2002, Accepted: 12 March 2002 RID="*" ID="*"The other members of the INCAT group are Jacques Aubry PhD, Institut de Biologie, INSERM Unit 463, 9 Quai Moncousu, 44 035 Nantes, France; Nicole Baumann MD, InSERM Unit 495, Salpetriere Hospital, 75 651 Paris, Cedex 13 France; Robert Hadden PhD, Michael Lunn, MD, Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, London SE1 9 UL, UK; Martin Knapp Phd, Personal Social Services Research Unit, London School of Economics and Political Science, Houghton Street, London WC2A 1AE, UK; Jean-Marc Léger MD, Pierre Bouche MD, Service d'Eplorations Functionelles de la Salpetriere, 47 Boulevard de l'Hospital, 75 651 Paris, Cedex 13, France; Radim Mazanec CSc, Charles University, 2^nd Medical School, University Hospital, V uvalu 84, Prague 5, Czech Republic; Nicoletta Meucci MD, Institute of Clinical Neurology, University of Milan, Ospedale Maggior-Policlinico, via Sforza, 20 122 Milan, Italy; Frans van der Meché PhD, Department of Neurology, Erasmus Medical Center Rotterdam, dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; and Klaus Toyka PhD, Universitat Würzburg, Josef-Schneider Strasse 2, 97 080 Würzburg, Germany Correspondence to Giancarlo Comi, MD     

Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized,placebo-controlled,double-blind trial

In a randomized, placebo-controlled, double-blind study, we investigated whether statins alter cholesterol metabolites and reduce Abeta levels in the cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In post hoc analysis, simvastatin significantly decreased Abeta40 levels in the cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes were not observed in more severely affected patients.     

Cerebellum and speech perception: a functional magnetic resonance imaging study

A variety of data indicate that the cerebellum participates in perceptual tasks requiring the precise representation of temporal information. Access to the word form of a lexical item requires, among other functions, the processing of durational parameters of verbal utterances. Therefore, cerebellar dysfunctions must be expected to impair word recognition. In order to specify the topography of the assumed cerebellar speech perception mechanism, a functional magnetic resonance imaging study was performed using the German lexical items "Boden" ([bodn], Engl. "floor") and "Boten" ([botn], "messengers") as test materials. The contrast in sound structure of these two lexical items can be signaled either by the length of the wordmedial pause (closure time, CLT; an exclusively temporal measure) or by the aspiration noise of wordmedial "d" or "t" (voice onset time, VOT; an intrasegmental cue). A previous study found bilateral cerebellar disorders to compromise word recognition based on CLT whereas the encoding of VOT remained unimpaired. In the present study, two series of "Boden - Boten" utterances were resynthesized, systematically varying either in CLT or VOT. Subjects had to identify both words "Boden" and "Boten" by analysis of either the durational parameter CLT or the VOT aspiration segment. In a subtraction design, CLT categorization as compared to VOT identification (CLT - VOT) yielded a significant hemodynamic response of the right cerebellar hemisphere (neocerebellum Crus I) and the frontal lobe (anterior to Broca's area). The reversed contrast ( VOT - CLT) resulted in a single activation cluster located at the level of the supratemporal plane of the dominant hemisphere. These findings provide first evidence for a distinct contribution of the right cerebellar hemisphere to speech perception in terms of encoding of durational parameters of verbal utterances. Verbal working memory tasks, lexical response selection, and auditory imagery of word strings have been reported to elicit activation clusters of a similar location. Conceivably, representation of the temporal structure of speech sound sequences represents the common denominator of cerebellar participation in cognitive tasks acting on a phonetic code.     

Morphological alterations in the amygdala and hippocampus of mice during ageing

Declines in memory function and behavioural dysfunction accompany normal ageing in mammals. However, the cellular and morphological basis of this decline remains largely unknown. It was assumed for a long time that cell losses in the hippocampus accompany ageing. However, recent stereological studies have questioned this finding. In addition, the effect of ageing is largely unknown in another key structure of the memory system, the amygdala. In the present study, we have estimated neuronal density and total neuronal numbers as well as density of fragments of degenerated axons in different hippocampal subfields and amygdaloid nuclei. Comparisons were made among aged (21-26 months old) mice and normal adult littermates (8 months old). No significant volume loss occurs in the hippocampus of aged mice. Small but insignificant reductions in total neuronal numbers were found in the hippocampus and in the amygdaloid nuclei. In contrast to the mild effects of ageing upon neuronal numbers, fragments of degenerated axons were increased in both hippocampus and amygdala of aged mice. These data suggest that ageing does not induce prominent cell loss in the hippocampus or amygdala, but leads to degeneration of axons that innervate these forebrain structures. Thus, mechanisms underlying age-related dysfunction depend on parameters other than neuronal numbers, at least in the hippocampal formation and the amygdala.