Liquorkomplement und Multiple Sklerose

Zusammenfassung 1. In 239 Liquores, darunter 47 MS-Fälle und 91 normale Kontrollen, wurden Komplement und Komplementfaktoren (C₁, C₂, C₃ und C₄) bestimmt.2. Im normalen Liquor ist in der Regel keine Gesamtkomplementaktivität vorhanden. Dagegen ist die C₁- wie C₄-Aktivität praktisch immer und C₂-sowie C₃-Aktivität in über der Hälfte der Fälle zu finden. Das Komplementmuster im Liquor ist daher im Gegensatz zum Serum unvollständig.3. Bei erhöhtem Eiweiß zeigt der Liquor dagegen häufig Gesamtkomplementaktivität. Je höher das Liquoreiweiß ist, um so höher ist der Gehalt an C₂, C₃ und Gesamtkomplement. Diese Beziehungen zwischen Gesamteiweiß und Komplementaktivität gelten für normalen wie pathologischen Liquor einschließlich der MS-Fälle.4. Im MS-Liquor sind C₂, C₃ und Gesamtkomplement seltener zu finden als bei den Kontrollen. Bei den MS-Patienten ist C₂ und C₃ im akuten Schub herabgesetzt. C₃ nimmt im Verlauf der Erkrankung wahrscheinlich ab.5. Mit Antikomplementserum wurde _1C-Globulin, ein Teilfaktor von C₃, im Liquor von 55 MS-Patienten und 42 Kontrollen bestimmt. Es besteht kein Unterschied zwischen MS und Kontrolliquor. Auch bei akut entzündlicher MS ist _1C nicht vermindert.6. In der Diskussion wird auf widersprechende eigene Befunde über _1C-Inaktivierung im Serum während der akut entzündlichen MS-Phase hingewiesen.

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Summary 1. Complement and complement factors (C₁, C₂, C₃ and C₄) were determined in 239 specimes of cerebrospinal fluid (CSF) including 47 cases of Multiple Sclerosis (MS) and 91 normal controls.2. In general, total complement activity is absent in normal specimens while that of C₁ and C₄ can be found practically always and that of C₂ and C₃ in more than half of the cases. Therefore, the pattern of complements in the CSF is incomplete as opposed to that of serum.3. In contrast, samples with increased protein content frequently yield total complement activity. The higher the protein content of CSF the higher the content of C₂, C₃ and total complement. This relationship between amount of total protein and complement activity applies both to normal and pathological CSF specimens including those from MS.4. In cerebrospinal fluid from patients with MS, C₂, C₃ and total complement are found less frequently than in that from controls. C₂ and C₃ are diminished in patients with an acute exacerbation of MS. C₃ decreases probably in the course of the disease.5. _1C-globulin, a component of C₃, was determined with anticomplement sera in specimens from 55 patients with MS and from 42 controls. There is no difference between CSF of MS and controls. Even in acutely inflammatory cases of MS, _1C is not diminished.6. Discussing his results the author points out discrepancies concerning the nactivation of _1C in serum during acutely inflammatory episodes of MS.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Vascular and electromyographic responses evoked in forearm muscle by isometric contraction of the contralateral forearm

There is controversy over whether isometric contraction of the forearm evokes vasoconstriction or vasodilatation in the muscles of the contralateral forearm. In the present study we have investigated in normal man, the effects of isometric contraction of one arm at 75, 50 and 25% maximum voluntary contraction (MVC) on arterial pressure, heart rate, blood flow and vascular resistance of the contralateral forearm and on electromyographic (EMG) activity recorded from that same arm with sensitive, surface electrodes.When EMG activity was not being recorded from the resting arm, isometric contraction of the contralateral arm for 2 min evoked increases in arterial pressure and heart rate whose magnitudes were graded with % MVC and an increase in forearm blood flow and a decrease in forearm vascular resistance at 75, 50 and 25% MVC, indicating vasodilatation. Further experiments in which EMG activity was recorded from the resting arm demonstrated that the decrease in forearm vascular resistance evoked by 75% MVC was associated with a substantial increase in EMG activity of the extensor and flexor muscles of that arm. By contrast, when forearm contraction was performed at 75% MVC whilst subjects viewed the EMG activity in the resting arm on an oscilloscope and kept EMG activity minimal, vascular resistance increased in that arm, indicating vasoconstriction. Further, when subjects performed contraction at 25% MVC whilst showing minimal EMG activity in the contralateral arm, vascular resistance in that same arm increased (from 78 ± 16 to 124 ± 29 mmHg/ml/min/100 ml tissue). These results are discussed in relation to those of previous studies. We propose, that in normal man, isometric contraction of the forearm evokes primary vasoconstriction in the muscles of the contralateral forearm, but that this response may be overcome by muscle vasodilatation occurring secondary to unintended muscle contraction or as part of the alerting response to acute stress.     

Chronic progressive and relapsing neuromyopathy with massive dilatations of endoplasmic reticulum in muscle fibers

Summary Large intracytoplasmic inclusions arising from the endoplasmic reticulum and nuclear envelope were found in the muscle fibers of a 32-year-old individual with a life-long, chronic and progressive sensory-motor neuropathy. The morphological features of the inclusions were similar to that occasionally reported in the striated muscles in several unrelated conditions as well as to hyaline or colloid inclusions commonly seen in motor neurons of the brain stem and spinal cord. The chemical nature of the inclusions is not known. Their occurrence in the muscle fibers is probably secondary to chronic denervation.     

The RAGE pathway in inflammatory myopathies and limb girdle muscular dystrophy

Oxidative stress and nuclear factor-B (NF-B) activation are linked to the pathogenesis of many metabolic, degenerative, and chronic inflammatory diseases. Activation of the receptor for advanced glycation end products (RAGE) by its specific ligand N-carboxymethyllysine (CML) results in the activation of NF-B and the production of proinflammatory cytokines. To determine whether engagement of RAGE contributes to the pathogenesis of inflammatory myopathies, we performed immunohistochemical studies on the presence of CML-modified proteins, RAGE and activated NF-B in muscle biopsies of patients with polymyositis (PM, n=10), dermatomyositis (DM, n=10), limb girdle muscular dystrophy (LGMD, n=10) and in 10 controls with normal muscle biopsy results. In inflammatory myopathies CML, RAGE and NF-B were detected in mononuclear cells and in regenerating muscle fibers. CML, NF-B and, to a lesser extent, RAGE were also found in degenerating muscle fibers, but colocalization of CML, RAGE and NF-B was only seen in infiltrating mononuclear cells and regenerating muscle fibers. Immunofluorescence double labeling demonstrated an expression of CML, RAGE and NF-B in CD4-, CD8-, CD22- and CD68-positive mononuclear cells. Western blot analysis showed an increased immunoreactivity for CML-modified proteins in PM and DM. In LGMD, CML, RAGE and NF-B were found in regenerating muscle fibers and less frequently in degenerating muscle fibers, and with lower staining intensities than in inflammatory myopathies. Our data suggests that the CML-RAGE-NF-B pathway is an evident proinflammatory pathomechanism in mononuclear effector cells in PM and DM. RAGE-mediated NF-B activation may be involved in muscle fiber regeneration in inflammatory myopathies and LGMD.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Does Ca2+ channel blockade modulate the antidepressant-induced changes in mechanisms of adrenergic transduction?

Summary We investigated how the L-type calcium channel blockade (CCB) with nifedipine affects the cyclic AMP responses to noradrenaline or isoproterenol in cerebral cortical slices from rats receiving antidepressant treatments that induce (electroconvulsive shock, imipramine) or do not induce (amitriptyline) -downregulation. To assess the role of protein kinase C (PKC) in receptor crosstalk under CCB conditions, the cyclic AMP responses were tested also in the presence of a PKC activator, TPA. CCB alone induced no changes, but modulated the action of those antidepressants that down regulate the -adrenergic system. Chronic ECS and imipramine treatments were differently affected. ECS, under conditions of CCB, down regulated the response to isoproterenol in the presence of TPA, while imipramine ceased to block the TPA-potentiation of cyclic AMP responses. Thus, CCB affects the processes related to the antidepressant-induced changes on the crosstalk between ₁- and -adrenergic receptors, depending on the specific properties of the antidepressant.     

„Fingerprint inclusions” in muscle fibres in dystrophia myotonica

Summary Fingerprint inclusions were observed in numerous muscle fibres of 3 cases of dystrophia myotonica studied by electron microscopy in two different laboratories. They consist of parallel or concentric palisades of short electron dense linear elements. Identical fingerprint inclusions were reported in two other clinical conditions and cannot therefore be regarded as specific for a particular muscle disease. Their origin and significance remain obscure.     

Types of authority and two problems of psychiatric wards

This paper concerns the relationship between authority structures and two problems reported in the literature as common to milieu or therapeutic community wards. Psychiatric wards with rational-legal and charismatic authority structures are found more likely to experience mood and morale swings on the part of patients and staff and to spend excessive time and energy changing ward rules.     

Die Bedeutung der diskontinuierlichen Zonierung des Immunglobulinbereiches für die Diagnose neurologischer Erkrankungen

Zusammenfassung 1. 340 Patienten, welche bei der agarelektrophoretischen Auftrennung der Liquorproteine eine diskontinuierliche Zonierung im Bereiche der -Globuline zeigten, wurden bezüglich Verteilung dieser clonalen -Zonen auf die verschiedenen neurologischen Erkrankungen untersucht.2. Bei der MS und den anderen entzündlichen neurologischen Erkrankungen findet sich eine Häufung der schnell wandernden Zone ₂ und der mittelschnell wandernden Zonen ₃ und ₄.3. Bei den Discushernien und den zentralnervös-nichtentzündlichen Erkrankungen ist die Zonenverteilung ziemlich flach und undifferenziert, wobei hier wie auch bei Tumoren und Polyneuritiden der relativ hohe ₀-Anteil auffällt als ein Phänomen, das bei zentralnervös-entzündlichen Prozessen nur selten anzutreffen ist. In den wenigen Tumorfällen mit -Zonierung scheint die ₄-Position deutlich zu überwiegen.4. In der Hälfte aller MS-Liquoren mit -Zonierung ist das Totalprotein, in einem Sechstel das Total--Globulin (rel%) normal, und nur bei zwei Dritteln finden sich Plasmazellen. Die elektrophoretische Feststellung von -Zonierung ist in der neurologischen Labordiagnostik folglich ein wichtiges Hilfskriterium.5. Mit zunehmendem Anstieg des -Globulin-Gehaltes im Liquor läßt sich bei MS-Patienten, nicht aber bei allen Krankheitsgruppen, eine Zunahme der Häufigkeit der -Zonierung nachweisen.6. Das Auftreten von -Zonierung ist bei den zentralnervös-entzündlichen Krankheiten und der MS sechsmal häufiger als bei den zentralnervös-nichtentzündlichen Krankheiten.7. -Zonierung scheint beim Gesunden, bei psychiatrischen Erkrankungen, Myopathien, bei gewissen Tumoren (Neurinomen) und metabolisch bedingten Polyneuritiden nicht vorzukommen.

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The significance of discontinuous zonation of electrophoretically separated globulins for the diagnosis of neurological diseases

Summary 1. 340 patients in whom discontinuous zonation of the globulin region was observed after electrophoretic separation of the CSF proteins were examined to see how the distribution of these clonal zones is correlated with different neurological diseases.2. In multiple sclerosis (MS) and other inflammatory diseases of the CNS, zones are most frequently found in the medium positions: ₂, ₃ and ₄.3. In disk hernias and the noninflammatory diseases of the CNS, the dispersion of zone frequency is rather undifferentiated. In these conditions and in tumors of the CNS and polyneuritis, the relatively high proportion of ₀ zones is a conspicuous feature; it is scarcely encountered in inflammatory processes of the CNS. The rare cases of tumors with zonation show a preponderance of the ₄ zone.4. The total protein content is normal in half of all MS fluids with zonation; in one sixth the relative amount of total globulin is also normal, whereas plasma cells are demonstrable in only two thirds. The electrophoretic evaluation of zonation is, therefore, an important tool in neurological laboratory work.5. Increased amounts of globulin in CSF are accompanied by an increased frequency of zonation in some diseases, such as MS, but not in tumors or vascular processes.6. The incidence of zonation is about 6 times higher in MS than in noninflammatory diseases of the CNS.7. zonation seems not to be present in healthy persons, in psychiatric diseases, myopathies, some tumors (neurinoma) and polyneuritis of metabolic-toxic etiology.

     

Acid maltase deficiency in non-identical adult twins

Summary Acid maltase deficiency is described in non-identical adult twins. The onset of the disease can be traced into late infancy; the clinical picture is one of severe muscular dystrophy; respiratory insuficiency was the cause of death in one case. The autopsy showed the central nervous system, heart and liver to be spared. Glycogen filled vacuoles are found in skin, mesenchymal cells, small nerves and skeletal muscles. The light microscopic study of 9 different muscles showed extremely variable involvement ranging from normal appearance to overt vacuolization. A 6–20% residual acid -glucosidase activity was found in visceral organs, cultured fibroblasts and in some skeletal muscles. No satisfactory explanation can be given why this generalized acid -glucosidase deficiency produces a selective involvement of skeletal muscles. If compared with infantile AMD (Pompe's disease) our cases have a much higher residual acid -glucosidase activity and show the presence of an antigenically detectable protein.From our study and from a similar report in the literature (de Barsy et al., 1975), it appears that a combined approach of light microscopy, electron microscopy and biochemical analysis (determination of acid -glucosidase) is necessary to make a diagnosis of AMD in adults.Dr. Th. de Barsy is a Research Fellow of the Fonds National de la Recherche Scientifique.     

Life events and syndromes of depression in the general population

Summary Brown and Harris (1978) contend that life events have causal significance for both psychotic and neurotic depression. This contradicts the psychiatric tradition. Neurotic depression has been regarded as a consequence of life-stress, while psychotic depression has been regarded as a consequence of processes intrinsic to the organism. Empirical evidence is presented to support the view that life events have a differential effect, within the general population. It is argued that Brown and Harris's (1978) conclusion follows from an inappropriate approach to classification. It is argued further that their data lend support to the traditional view. It is noted that their approach may inhibit the development of explanatory models linking life-stress, vulnerability factors and depression.     

Effect ofd,l-α-aminoadipate on the mediobasal hypothalamus and endocrine function in the rat

Summary Using the glutamate analog,d,l--aminoadipic acid (d,l-AA), experiments were conducted to examine the nature, extent, and specificity of its toxicity in the mediobasal hypothalamus and to determine its effect on endocrine homeostasis. Neonatal rats received daily injections ofd,l-AA (4 g/kg BW) on postnatal days 5–10 and were killed at various post-treatment intervals. Sex-matched littermates were given equimolar amounts of NaCl and served as controls. Treated rats killed 18 days post injection weighed slightly less than controls and had reduced testicular, ovarian, and uterine weights, but the differences were not statistically significant. Ind,l-AA treated rats serum and pituitary levels of TSH and PRL were comparable to control values. Pituitary content of LH ('s and 's) and FSH ('s), however, was lower (P<0.05) ind,l-AA treated rats than in controls, but serum levels were not significantly different. Distinct cytopathologic changes were evident in the arcuate nucleus and median eminence ofd,l-AA-treated rats killed at 2 and 6 h post injection only. By 12 h evidence of acute damage had largely disappeared. Both glial and ependymal cells underwent edematous swelling and necrosis, but neurons were largely unaffected. Evidence of reactive changes, such as gliosis, infiltration of microglia, and removal of debris, however, were not very conspicious. A random sample of mediobasal hypothalami of rats killed 18 days post injection failed to show any detectable lesion or residual effects of earlier pathology. Age at the time of exposure to the gliotoxin was found to be an important variable affecting both extent and duration of injury. The most deleterious effects were observed when the gliotoxin was administered in the form of a single injection on postnatal day 5 only. The results suggest that normal neuronal activity and endocrine homeostasis, specifically gonadotropin, may be irreversibly altered as a consequence of transient disruption of the glial compartment.Supported by grants from the Medical Research Council of Canada, the St. Boniface General Hospital, and Mrs. James A. Richardson Research Foundations     

Identification of the κ and λ light chains within the CSF immunoglobulin region in multiple sclerosis and subacute sclerosing panencephalitis by immunofixation after isoelectric focusing

Summary The distribution of the and light chains within the cerebrospinal fluid (CSF) IgG oligoclonal bands of 15 multiple sclerosis (MS) and 3 subacute sclerosing panencephalitis (SSPE) patients has been studied by isoelectric focusing (IF) followed by direct immunofixation. The oligoclonal bands demonstrated by IF were both homogeneous and heterogeneous with regard to the light chain type; in the MS patients there was a prevalence of heterogeneous bands and of homogeneous bands of type, while in SSPE a slight prevalence of homogeneous bands was found. The homogeneous bands were preferentially disposed in a more cathodal position in respect to IgG bands; in some cases bands probably constituted only of free light chains of type were found. Finally, in some cases, the oligoclonal IgG pattern was more distinct after immunofixation than after basal IF.

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Zusammenfassung Die Verteilung von leichten - und -Ketten in den oligoklonalen IgG-Fraktionen des CSF ist bei 15 MS- und 3 SSPE-Patienten durch isoelektrische Fokussierung (IF) und anschließende direkte Immunofixierung untersucht worden.Die durch IF hervorgehobenen oligoklonalen Fraktionen waren sowohl homogen als auch heterogen hinsichtlich des Typs der leichten Ketten; bei den MS-Patienten waren die heterogenen und homogenen IgG-Fraktionen des Typs vorherrschend, während bei den SSPE-Patienten die homogenen IgG-Fraktionen des Typs leicht vorherrschend waren.Die homogenen IgG-Fraktionen des Typs waren im Vergleich zu den IgG-Fraktionen des Typs vorzugsweise in einer kathodennaheren Position angetroffen worden; in einigen Fällen wurden IgG-Fraktionen gefunden, die wahrscheinlich nur aus freien leichten Ketten des Typs bestehen.Schließlich waren in einigen Fällen die oligoklonalen IgG-Fraktionen nach der Immunofixierung deutlicher als nach der IF.

     

Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner

Different types of amyloid -protein (A)-containing plaques occur in brains of Alzheimers disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the A peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is involved in A transport and clearance, and the 4-allele of the apolipoprotein-E gene (APOE) is a major risk factor for sporadic AD, it is plausible to speculate that apoE plays a pathophysiological role in the initiation of A deposition. To address the issue of whether binding of apoE to A is involved in initial A deposition, we studied the human medial temporal lobe of 60 autopsy cases encompassing the full spectrum of AD-related pathology. In temporal lobe regions, which become involved for the first time at a given stage of -amyloidosis, all plaques represent newly formed plaques, and these were studied with immunohistochemical methods. ApoE was present in 36 cases, and was frequently co-localized with newly formed A deposits detectable with anti-A₄₂ but not with antibodies raised against N-terminal epitopes of A. In 10 additional cases, immunoreactivity against apoE was completely lacking in newly formed plaques, which, at the same time, displayed immunoreactivity against N-terminal epitopes of A. The failure of N-terminal epitopes of A to co-localize with apoE in newly formed plaques indicates that these deposits presumably contain apoE-A complexes, in which the N-terminal epitopes of A are often concealed after complexing with apoE, thus preventing subsequent binding of antibodies. Moreover, apoE-positive newly formed plaques were seen more frequently in APOE 4/4 cases than in non-APOE 4/4 individuals, thereby underlining the potentially crucial role of apoE for the development of A deposits.     

Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma

Objectives This study analyzed the intratumoral activity of interferon alpha (IFN-) in the treatment of cystic craniopharyngiomas.Patients and methods From January 2000 to January 2004, nine patients presenting with cystic craniopharyngiomas were treated with intratumoral injection of IFN- at the Pediatric Oncology Institute of the Federal University of São Paulo–Escola Paulista de Medicina. Age ranged from 1 year and 10 months to 18 years (mean 10 years). All intratumoral catheters were inserted by a subfrontal approach. Doses varied from 36 to 108 MU.Results There was complete disappearance of the lesion in seven cases. In two cases, partial reduction of tumor size was observed at follow-up. Follow-up varied from 1 year to 3 years and 6 months (mean 1 year 8 months).Conclusions IFN- proved to be an effective drug in the control of cystic craniopharyngiomas. Additional studies should be carried out to determine the optimal dose of IFN- in the treatment of cystic craniopharyngioma. In addition, other drugs possessing high efficacy and low neurotoxicity should be analyzed.     

Ganglioside mapping of a human medulloblastoma xenograft

Summary The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II³--NeuAc-LacCer (GM3) and II³--NeuAc-GgOse₃ Cer (GM2) but there were also relatively large proportions of IV³--NeuAc-LcOse₄Cer (3-isoLM1), IV³--NeuAc-nLcOse₄Cer (3-LM1) and a further ganglioside of the neolactoseries with an extra lactosamine moiety. The only oligosialoganglioside detected was IV³, II³--NeuAc₂-GgOse₄Cer (GD1a).Abbreviations: The gangliosides have been designated according to Svenerholm [18] GM3 II³--NeuAc-LacCer - GM2 II³--NeuAc-GgOse₃Cer - GM1 II³--NeuAc-GgOse₄Cer - 3-LM1 IV³--NeuAc-nLcOse₄Cer - 3-isoLMI IV³--NeuAc-LcOse₄Cer - Fuc-3-isoLMI IV³--NeuAc, III⁴-Fuc-LcOse₄Cer - GD1a IV³, II³--NeuAc₂-GgOse₄Cer - FAB-MS Fast atom bombardment-mass spectometry - GC-MS gas chromatography-mass spectometry Supported by NC1 RO1 CA11898 to Dr. Bigner and B8803X-00627-24B from the Swedish Medical Research Council to Dr. L. Svennerholm     

The selling of community mental health

The author criticizes what he considers to be the golden rhetoric, questionable statistics, and even more questionable practices of The Movement.Although the article leans heavily toward pessimism and will therefore irritate many readers, Dr. Steinhart's warning deserves serious consideration. Certain it is that rampant over-optimism can lead to big trouble, as David Halberstam has documented with regard to the evaluations of our Saigon experts in the early 60s.     

Regional serotonin transporter availability and depression are correlated in Wilson’s disease

Summary. In patients with Wilsons disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [¹²³I]-2-carbomethoxy-3-(iodophenyl)tropane ([¹²³I]-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [¹²³I]-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients.Received December 10, 2001; accepted March 24, 2003 Published online June 10, 2003     

Visuoperception and visuospatial and visuorotational performance in Parkinson's disease

Summary Forty patients with Parkinson's disease were compared with 33 normal controls with respect to their performance in the Wechsler Adult Intelligence Scale subtests information, similarities, block design, and picture completion, in a test for visual neglect (Hamsher's line cancellation test) and in tests for visuospatial and visuorotational abilities (cube task from Amthauer's intelligence structure test and Rybakoff figure test, as revised by Meili). The findings show that the patients scored significantly worse than the controls (Mann-WhitneyU test,P=0.004) in the Rybakoff figure test, testing visual concept finding, imagination and visual rotation. In the other tests no significant differences were found between the patients and the controls. The deficit of the patients in the figure test of Rybakoff correlated significantly with tremor (P=0.013), akinesia (P=0.009), disability (P=0.043), and age (P=0.004, Spearman rank correlation).     

Dose-dependent pharmacokinetics of α-methyl-p-tyrosine (α-MT) and comparison of catecholamine turnover rates after two doses of α-MT

Summary Groups of rats were injected i.p. with 0.407 or 1.02 mmoles/kg of D, L--methyl-p-tyrosine methylester HCl (-MT). The time-courses for-MT in plasma and brain were followed together with the endogenous brain dopamine (DA) and noradrenaline (NA) contents.The elimination of-MT from plasma and brain was markedly delayed after the high-MT dose compared with the low dose. At 40 hours after the injection of 1.02 mmoles/kg of-MT both plasma and brain levels were high, whereas no-MT could be detected in plasma or brain at 16 hours after the lower dose.The brain catecholamines were decreased to very low values after the higher-MT dose (DA 14% and NA 10% of controls at 8 and 24 hours respectively). There was no complete recuperation at 40 hours of any of the amines. After the lower-MT dose, the DA concentration was back to control levels at 16 hours and NA at 12 hours. Between 16–40 hours after the high-MT dose a majority of the rats showed prominent signs of sedation, weight loss and dehydration. No such signs were observed in rats receiving 0.407 mmoles/kg. During the first hour after the-MT injection the declines of DA and NA respectively were almost identical for both-MT doses. When the whole time-course (0–8 hours) after the high dose was considered, biphasic declines were obtained for both DA and NA, suggesting at least two different catecholamine pools. However, due to toxic effects after the high-MT dose, turnover data have to be interpreted with caution.