The phenylalanine loading test in the differential diagnosis of dystonia.

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients with DRD and patients with other types of dystonia was observed. This indicates that Phe-L may be helpful in the differential diagnosis of dystonias.

mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours.

BACKGROUND: Insulin-like growth factors (IGF) and their corresponding receptors and binding proteins are important in carcinogenesis for several tumours, but their expression pattern in the functionally and biologically heterogeneous human neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown. MATERIALS AND METHODS: This study searched for the mRNA expression patterns of components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF-2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours associated with carcinoid syndrome and functionally inactive tumours) employing reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the 37 tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP-2 was found in all tumour samples while the IGFBP-1 was expressed only at low frequency (10-22%) among the four tumour types. The IGF-2R was predominantly expressed in gastrinomas. Among the four tumour types the expression of IGF-1R, IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <--> IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <--> IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <--> IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6). CONCLUSIONS: The described differences of the expression patterns of the IGF system components in neuroendocrine tumour subtypes suggest tumour type-dependent different pathways in tumour growth control by IGF system components.

[Coping behaviors in Parkinson's disease]. / Krankheitsverarbeitung bei Morbus Parkinson.

In 45 patients with Parkinson's disease, we investigated coping behavior and its correlations to demographic and disease-related data, locus of control, depression, and psychosocial adaptation. Active, problem oriented, and self-reorganizing strategies were predominantly used and regarded as especially helpful by the 27 men and 18 women (age: 56 years; duration of illness: 9 years). While age and sex were not associated with coping, external locus of control correlated positively to "depressive coping" and duration of illness correlated negatively to "distraction and self-affirmation." Coping strategies regarded as maladaptive and a small degree of internal locus of control correlated to unfavourable results for depression and satisfaction.

Influence of a high-speed polymerization method on the marginal integrity of composite fillings in Class-II cavities.

The aim of this study was to evaluate the effect of a rapid photopolymerization method on the marginal integrity of composite fillings. Ninety two-surface cavities were prepared in extracted human molars using the SonicSys preparation system. All cavities were bonded with one bonding agent (Syntac) and filled with a microfilled composite (Herculite XRV), a heavy filled composite (Z100 MP), and an Ormocer (Definite) in two increments. Each increment had a thickness of approximately 1.5 mm and was polymerized using either halogen light or the plasma light of Apollo 95 E. In this process, six trial groups each containing 15 fillings were created. After replicas were made, the test teeth were subjected to a thermocycling process of 2000 temperature cycles (5 degrees C/55 degrees C) followed by a wear simulation of 50,000 stress cycles each with 50 N. This was followed by the creation of a second set of replicas, quantitative margin analysis, and dye penetration. A significant (P < 0.05) influence of the thermomechanical stress and a significant (P < 0.05) influence of the factor "material" were shown for the margin criterion "continuous margin" using MANOVA. The factor "light source" produced no significant influence (P = 0.57) on the amount of continuous margin. During the dye penetration, no significant differences between the polymerization methods could be established with the materials Herculite XRV and Z100 MP (H-test according to Kruskall and Wallis). Only with the material Definite was a significantly higher dye penetration observed at the occlusal measuring point in the plasma light group. A rapid polymerization with high light intensity had no adverse effects on the margin quality within the limitations of this in vitro study. However the marginal integrity might have been influenced by the chosen adhesive system/composite resin combination, which does not represent the respective product line. Additionally, further studies ought to show which exposure time is necessary for a sufficient degree of conversion.

Longevity of oroincisal ceramic veneers on canines--a retrospective study.

PURPOSE: The longevity of oroincisal veneers on canines of IPS-Empress ceramic for the restoration of lost canine guidance was determined in a retrospective study. MATERIALS AND METHODS: Since 1992, all ceramic restorations made in the Department of Operative Dentistry have been entered in a data base. In that time period, 17 patients with 36 oroincisal veneers on canines to restore lost canine guidance have been documented. The survival rate of the restorations was calculated with the Kaplan-Meier method. RESULTS: The mean follow-up period was 6.74 years. The 6.5-year survival rate was 76%. The 6.5-year survival rate of canine oroincisal ceramic veneers in the maxilla was 74%, and in the mandible 78%. The difference in the survival rate of maxillary and mandibular restorations was not statistically significant. In the follow-up period, 8 of the 36 IPS-Empress canine veneers failed. Reasons for failure were ceramic fracture, fracture of the adhesive bond, and loss of function. CONCLUSION: In view of the longevity, the excellent properties of the IPS-Empress ceramic material, i.e., minimum abrasion of the opposing teeth, and good esthetics, we consider the restoration of lost canine guidance using this technique a viable alternative to the classical precious-metal pinledge or composite buildup.

Flow cytometry of cerebrospinal fluid (CSF) lymphocytes: alterations of blood/CSF ratios of lymphocyte subsets in inflammation disorders of human central nervous system (CNS).

Flow cytometry was adapted to measure lymphocytes in human cerebrospinal fluid (CSF). The method was sufficiently precise, reproducible and accurate despite low cell counts. In lumbar CSF of controls with 500 to 3500 (10(3)/l) leukocytes, lymphocyte counts correlated with those in corresponding venous blood: blood/CSF ratios of approximately 2000 : 1 were found for total T cells (CD3+) and CD3+ HLA-DR-, CD3+4+, CD3+8+ subsets, ratios were increased for the lymphocyte subsets CD3+ HLA-DR+ < or = CD3+16+56+ < CD16+56+3- < CD8+3- << CD19+; CD8+4+ ratio was half of CD3+ ratio. Data indicate selective barriers (blood-brain and blood-CSF barriers) to blood lymphocyte subsets which favor the transfer of T subsets. Correlation of the subset ratios to the CD3+ ratio indicates distinct barrier properties which changed differently with acute and subacute inflammations and neuroimmunological diseases of central nervous system (CNS) in lumbar or ventricular CSF, but not with simple protein barrier disturbance. HLA DR+ T ratios were higher than HLA DR- T ratios only with controls and some neuroimmunological diseases. Lymphocyte barrier characteristics were related to protein leakage situated at the same barriers, indicating for the lymphocyte subsets selective transfer routes in control subjects and non-selective routes in patients with CNS inflammation where altered ratios revealed a mixture of both routes.

Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours.

BACKGROUND: Human gastroenteropancreatic neuroendocrine tumours are functionally and biologically heterogeneous, but their exact growth factor receptor expression pattern, important for onco- and carcinogenesis, remains unknown. METHODS: This study searched for the mRNA expression pattern of six tyrosine- and serine/threonine kinase receptors [hepatocyte growth factor (HGFR), fibroblast growth factor (FGFR), epidermal growth factor (EGFR), insulin-like growth factor (IGF)-1R, transforming growth factor (TGF)-betaR1, TGF-betaR2] together with the five somatostatin receptors in human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours with carcinoid syndrome, functionally inactive neuroendocrine tumours) using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: EGF receptor was expressed almost exclusively in gastrinomas. Among the four tumour subtypes, expression frequencies of the somatostatin receptors 1 and 5, HGF-, IGF-1-, TGF-betaR1, TGF-betaR2 and the EGF-receptor varied significantly. CONCLUSIONS: In spite of the common cellular origin of these tumours, differences in growth factor receptor expression suggest the existence of different pathways during tumour subtype development.

In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat.

The action of the amantadine derivative memantine on the dopamine metabolism in the striatum and the n. accumbens of the rat was studied in vivo with different voltammetrical techniques. It was shown by differential pulse voltammetry that memantine enhanced extracellular levels of dopamine (DA) in the striatum of the anaesthetized rat, whereas an increase of 3,4 dihydroxyphenylacetic acid (DOPAC) could be observed only under freely moving conditions using square wave voltammetry. Under chloral hydrate anaesthesia the effect of memantine on extracellular DOPAC levels in the striatum and the n. accumbens was compared with MK-801, a well-known non-competitive NMDA-antagonist. Memantine did not affect striatal DOPAC concentrations under these conditions whereas MK-801 reduced the DOPAC signal. In the n. accumbens memantine enhanced the levels of extracellular DOPAC, while after MK-801 the signal was only slightly different from control. These findings suggest that in addition to its NMDA receptor antagonism, memantine affects dopaminergic transmission also by other mechanisms.

Laboratory diagnosis of radicular and pseudoradicular syndromes in cerebrospinal fluid (CSF): reliability of methods in consideration of pathogenetic aspects. Report on section "CSF diagnosis" of 4th Klagenfurter Neurology Workshop Conference on radicular and pseudoradicular syndromes, Klagenfurt, Austria, August 28-29, 1992.

Laboratory tests may be used to confirm the clinical differentiation of pseudoradicular syndromes and radicular syndromes. In the presence of pseudoradicular syndromes, CSF and blood samples yield no positive results with either non-specific or specific methods. Radicular syndromes give rise to positive findings; using non-specific methods they can be subdivided into inflammatory and non-inflammatory forms, with and without blood-nerve barrier impairment. Non-specific quantities of CSF routine diagnosis are total protein, albumin, leukocyte counts and differential cell count, L-lactate, intrathecal -IgG, -IgA, -IgM and immunoglobulin-class oligoclonal bands. Oligoclonal bands enable the highly sensitive differentiation of non-inflammatory from subacute-chronically inflammatory forms of radicular syndromes. Most of the specific quantities are the subject of current research, e.g. bacterial antigens, D-lactate, cultivation tests, polymerase chain reaction tests and pathogen-specific oligoclonal bands. Pathomechanisms affecting the permeability of the blood-nerve barrier to increasing concentrations of protein and to leukocyte subsets possibly explain the CSF findings in radicular and pseudoradicular syndromes.

Age-related alterations of the blood-brain-barrier (bbb) permeability to protein molecules of different size.

Transfer processes of differently sized protein molecules across the blood-brain-barrier (bbb) were studied in "normal" , respectively, diseased elderly humans. Lumbar CSF/serum ratio of albumin contents increased significantly with age in a control group, but it was diminished in patients suffering from inflammatory or non-inflammatory diseases. Ratio of alpha 2-macroglobulin contents increased with age, especially in the diseased elderly. Concentration ratios of lysozyme, orosomucoid, lactoferrin, IgG, IgA and IgM decreased with age in a control group and especially decreased in a patient group. The data are discussed with respect to two different transfer processes which appeared to be altered in age and/or disease processes.

Transport and production of cerebrospinal fluid (CSF) change in aging humans under normal and diseased conditions.

In three control groups of lumbar (L), cisternal (C), and ventricular (V) cerebrospinal fluid (CSF) with prealbumin contents of ventricular origin (CSF-V-prealbumin) within the reference range, indications for an increased transport of V-CSF into spinal space are presented in the elderly as well as an elevated production of V-CSF. Indications for a diminished V-CSF production, respectively, an increased transport of CSF-V-prealbumin into the spinal space were found in elderly patients suffering from diverse CNS diseases. As these alterations proved to be not disease-specific, the age-related increase of CSF transport was discussed with respect to brain atrophy and enlarged CSF spaces in the elderly central nervous system (CNS). CSF serum prealbumin content, an indicator of blood-brain-barrier function, increased with age similarly to albumin in the "normal" elderly, respectively with diverse CNS diseases. Age- and disease-related decreases of albumin and prealbumin contents in blood serum may lead to wrong interpretations.

Metformin-induced changes in serum lipids, lipoproteins, and apoproteins in non-insulin-dependent diabetes mellitus.

Forty patients with NIDDM and hyperlipoproteinemia were selected for a 12-week double-blind placebo-controlled trial to study the effects of metformin on lipoprotein concentration and composition. A significant decrease occurred in VLDL-apo B and all lipid components of VLDL, indicating a decreased number of circulating VLDL, while LDL-apo B was unchanged. Moreover in VLDL the relative TG content increased, the cholesterol content decreased, while in LDL the TG content decreased and the cholesterol content increased, indicating a change in the particle distribution over the spectrum VLDL-IDL-LDL. The initially enhanced TG-content in HDL was reduced. While a reduction in VLDL is observed together with improving glucose control irrespective of the applied method, the observed compositional changes in VLDL and LDL have not been described before and seem to be metformin-specific.

Changes with age in leucocyte counts, protein and IgG content of lumbar cerebrospinal fluid (CSF) of patients with inflammatory, ischemic, and hemorrhagic diseases or tumors of the central nervous system (CNS).

Parameters of blood-brain barrier (BBB) function and of humoral and cellular immune response were determined in lumbar CSF and blood serum samples from 717 patients and statistically compared to "healthy" controls (n = 190). Leucocyte counts (mainly mononuclear cells), total protein and IgG levels in CSF were significantly higher, and prealbumin fraction mostly lower in patients, besides other alterations of protein electrophoresis. Serum fractions (median) of protein electrophoresis were within the reference range. When parameters were correlated with age, a significant increase of total protein of 1.62 mg/dl and of IgG of 0.13 mg/dl per 10 years of age was found in lumbar CSF of controls. Elevated leucocyte counts did not correlate with age of patients, but they increased significantly with age, with respect to controls, to a higher extent in patients with polyneuritis, ischemia and injury; they decreased in patients with brain tumors and polyneuropathy. When compared to controls, elevated total protein levels significantly increased with age only with tumors and injury patients. In multiple sclerosis, IgG increased and beta-globulin fraction decreased significantly in CSF with age. The findings point to age-dependent alterations of BBB and immune response only in some patients groups which were different from those of controls.

Circadian rhythm of serotonin binding in rat brain--I. Effect of the light-dark cycle.

High affinity serotonin binding to rat brain membranes showed a circadian rhythm with minimal binding at 1000 and a maximal binding at 0000. Brain serotonin levels were almost inverse to the rhythm of serotonin binding. Under reverse light-dark conditions, lights on from 1900 to 0700, a significant phase shift in serotonin binding and concentration of about 8-10 hr was found. The adaptation of the rats to the inverse light-dark cycle was ascertained by plasma ACTH and corticosterone assay.

Circadian rhythm of serotonin binding in rat brain--II. Influence of sleep deprivation and imipramine.

Sleep deprivation (SD) modified the circadian rhythm of specific high affinity serotonin (5-HT) binding to rat brain membranes. In control rats a 24-hr rhythm was evident with a trough at 1000-1200 and a nadir at 0000. During the last 26 hr of a 49 hr SD period, trough and peak values were delayed by 4-6 hr. The 24-hr mean binding was significantly (P less than 0.001) different from that of controls. If sleep deprivation was followed by recovery sleep (RS), the normal rhythm of 5-HT binding was obtained already within 1 hr after SD. The effects of SD and RS were ascertained by plasma ACTH and corticosterone assay. No significant change in the hormone rhythms were observed through the mean plasma level of ACTH and corticosterone were enhanced to about 180 and 150%, respectively. Chronic treatment with the antidepressant imipramine resulted in a decrease of the 24-hr mean 5-HT binding by about 50% and a 2-hr delay of peak and trough values. Imipramine treatment decreased the peak value of 5-HT concentration at 1000 to about 65% and appears to abolish the rhythm of 5-HT concentration.

Lipoprotein fractions, lipoprotein lipase and hepatic triglyceride lipase during short-term and long-term uptake of ethanol in healthy subjects.

In short-term experiments, healthy fasting persons were given a basic dose of 0.5 g of ethanol/kg body weight, followed by hourly maintenance doses of 0.15 g of ethanol/kg body weight. After 10 h there was a significant increase of triglycerides in the VLDL, LDL, and HDL, the main rise (from 42 to 92 mg/dl) being found in the VLDL triglycerides. Other subjects, who received nourishment isocaloric with ethanol, likewise showed a significant rise of triglycerides in all lipoprotein fractions. Chylomicron triglycerides increased from 9.3 to 35.5 mg/dl. There was no significant change in postheparin HTGL, but postheparin LPL activity decreased after 10 h from 17.9 to 12.2 mmol FFA/ml/h in the fasting subjects, and from 28.5 to 10.2 mmol/FFA/ml/h in the persons receiving food. In long-term experiments after 4 weeks of 70 - 80 g of ethanol and isocaloric food daily, triglycerides increased, especially in the VLDL (from 50 to 82 mg/dl). The increase in the HDL, however, was also significant. After 4 weeks of ethanol, the chylomicron triglycerides in the plasma of the fasting subjects reached a value of 29.3 mg/100 ml, LDL cholesterol decreased, and HDL cholesterol increased. After 4 weeks of ethanol there was an increase in the lipoprotein lipase of the adipose tissue.

[Experimental studies on hemolysis in transurethral interventions]. / Experimentelle Untersuchungen zur Hämolyse bei transurethralen Eingriffen.

The question whether distilled water can be used as irrigating fluid for the transurethral electroresection has repeatedly given occasion for discussion. Price and better visibility when resecting speak in favour of its application. Haemolytic alterations, however, might occur and seem to make its application dangerous. Our own experiments in animals show that especially blood haemolised through distilled water in the bladder (a mixture of aqua dest. and haemolised erythrocytes) has a strong haemolytic effect. Intravenous instillation of distilled water leads to haemolytic processes as well, which, however, are weaker than those occurring after instillation of erythrocytes haemolised through distilled water. Solutions of Sorbitol and Manitol (e.g. Purisole) had no measurable haemolytic effect. On the basis of our examinations we can retain the fact that with massive absorption of already haemolised erythrocytes, dangerous alterations, occur. Such alterations depend on duration of resection, technique of resection and pressure conditions (use of low pressure irrigation resectoscopes or trocar irrigation). For the experienced urologic surgeon these factors might be less relevant, for the beginner, however, who might not take into consideration the facts mentioned, results could be disastrous. The use of Sorbitol- and Manitol-fluids during TUR, prevents haemolytic incidents with certainty.

[Longterm therapy and etofibrate (author's transl)]. / Langzeittherapie mit Etofibrat.

The stabilization parameters of patients under routine care are differentiated. 20 hyperlipoproteinemic patients (types IIa, IIb and IV) who were difficult to stabilize were treated with 0.9 g etofibrate daily. In addition to the cholesterold and triglyceride levels, we followed up the laboratory control parameters in the serum, fasting blood sugar and differential blood count. During the treatment period the cholesterol levels fell to 18%, triglycerides to 50%. Tachyphylaxis was never seen. The good tolerance of etofibrate shows that the substance is suitable as a potent hypolipidemic agent for longterm treatment of hyperlipoproteinemia.

Long-term treatment of hyperlipoproteinemia with etofibrate: clinical observations.

We investigated the changes in serum lipid concentrations of patients treated with Etofibrate as part of their routine management in the metabolic ambulatory care unit of the Medical Policlinic at the University of Marburg. In our study, 26 patients who had not responded well to prior treatment for Types IIa, IIb, III and IV hyperlipoproteinemia were given a daily dose of 900 mg Etofibrate for up to 48 months. As a result to this treatment, serum total cholesterol levels fell by up to 17,6% and triglyceride levels by up to 47,8%. We observed no tachyphylaxis toward Etofibrate. The results of standard laboratory parameters measured in parallel with drug treatment reflect a good tolerance for Etofibrate. This substance is highly suited as a potent lipid-lowering agent.