[Validation of a short test (3MS-R) for detecting Alzheimer's disease]. / Validierung eines kurzen Testverfahrens (3MS-R) für die Erkennung der Alzheimer-Demenz.

BACKGROUND: The Modified Mini-Mental State Examination-revised (3MS-R) is a brief cognitive test designed to detect cognitive impairment, which is often used in Canada and USA. OBJECTIVE: To assess the accuracy of the 3MS-R in identifying Alzheimer's disease (AD) in comparison with the conventional Mini-Mental State Examination (MMSE) in a German-speaking population. SUBJECTS: The study refers to 31 patients with early AD and 5 patients with moderate dementia of AD etiology, as well as to 46 age-matched cognitively normal participants. METHOD: The 3MS-R and the MMSE were validated against an expert diagnosis based on a comprehensive diagnostic workup. The 3MS scores were adjusted for educational attainment. Statistical analysis was performed using the Receiver Operating Characteristics (ROC). RESULTS: ROC curves demonstrated the superiority of the ACE over the MMSE in identifying AD (Area under the Curve: 3MS-R vs. MMSE: 0.995 vs.0.953). The optimal cut-off score for the 3MS for detecting AD was 88 and had a sensitivity of 98% and a specificity of 94%. The German version of the 3MS-R is a short and practical but accurate test battery for the identification of AD. The effectiveness of the German version of the test in detecting other forms of dementias or mild cognitive impairment could be a task for future studies.

Validation of the Addenbrooke's cognitive examination for detecting early Alzheimer's disease and mild vascular dementia in a German population.

We assessed the diagnostic accuracy of the German version of the Addenbrooke's Cognitive Examination (ACE) in identifying early Alzheimer's disease (AD) and mild vascular dementia (VaD) in comparison with the conventional Mini-Mental State Examination (MMSE). The study refers to 50 patients with mild dementia of AD, 26 patients with mild dementia of vascular etiology and to 54 cognitively normal subjects. The ACE and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic workup. Statistical analysis was performed using the receiver operator characteristics method. The optimal cut-off score for the ACE for detecting dementia in patients with early AD was 85/86, which had a sensitivity of 93% and a specificity of 86%. The optimal cut-off for the ACE for the identification of dementia in patients with mild VaD was also 85/86 and it had a sensitivity of 93% and a specificity of 100%. The kappa values imply a substantial agreement between the diagnoses made by the ACE and the MMSE. The German version of the ACE is a short and practical but accurate test battery for the identification of AD and VaD, assessing a broad range of cognitive functions and providing a wide profile of cognitive functions/dysfunctions.

[Effect of aceclofenac on thyroid hormone binding and thyroid function]. / Auswirkungen von Aceclofenac auf die Schilddrüsenhormonbindung und Schilddrüsenfunktion.

Influences of non-steroidal anti-inflammatory drugs (NSAID) on concentrations of thyroid hormones are known for a long time. These effects could be explained with interference between NSAIDs and thyroid hormone binding. We investigated the effects of a single dose of aceclofenac on thyroid function and thyroid hormone binding in 18 healthy volunteers. Serum levels of free thyroid hormones (FT3, FT4) and thyrotropin (TSH) were measured with commercial available kids and thyroid hormone binding was estimated with a specially modified horizontal argarose-gel-electrophoresis prior to and 2 hours after receiving a single dose of aceclofenac. We found a significant decrease in T3 binding on TBG and a significant increase of albumin-bound T3. All other investigated thyroid hormone binding parameters, FT3 and FT4, showed no significant changes. We conclude that aceclofenac leads to a significant redistribution of T3 protein binding. These effects seem to be explained by T3 displacement from TBG induced by aceclofenac.

[Increased occurrence of autoimmune thyroiditis in patients with chronic rheumatoid arthritis]. / Gehäuftes Auftreten der Immunthyreoiditis bei Patienten mit chronischer Polyarthritis.

The frequent occurrence of both rheumatoid arthritis and autoimmune thyroiditis was already investigated with in part many conflicting results. We investigated a number of 792 patients (383 of them suffering from rheumatoid arthritis and 409 with osteoarthritis). In all patients antithyroid peroxidase and antithyroglobulin antibodies were determined. Patients with rheumatoid arthritis showed a significantly higher occurrence of circulating thyroid antibodies than those with osteoarthritis (9.1% versus 3.7%, p = 0.0016). We conclude that there exists a cumulate coincidence of both diseases. Patients suffering from rheumatoid arthritis should undergo a thyroid examination especially for the presence of autoimmune thyroiditis.

[Quantitative scintigraphy of the sacroiliac joints]. / Quantitative Szintigraphie der Ileosakralgelenke.

Effects of gender and age on quantitative sacroiliac joint imaging are discussed controversially. In most investigations the number of controls has been small and might not exactly reflect the change of sacroiliac/sacral (SI/S) ratios related to different age and gender. The aim of our study was to evaluate the changes SI/S ratios according to age and gender. In 125 patients without any history of either diseases or complaints of the sacroiliac joints a bone scintigraphy was obtained and the SI/S ratios were calculated. We observed a significant negative correlation of SI/S index with age. After separation into 4 different age groups a significant decline of the ratios could be shown. There were no significant differences between male and female patients. We conclude that the influence of age on SI/S ratios is substantial. But also many other factors like patient position, algorithm of SI/S ratio calculation, the time interval between application of the radiopharmaceutical and data acquisition may exert effects on SI/S ratios. It seems necessary for each department to evaluate their own age related reference values of SI/S ratios.

A Rhizobium leguminosarum mutant defective in symbiotic iron acquisition.

Iron acquisition by symbiotic Rhizobium spp. is essential for nitrogen fixation in the legume root nodule symbiosis. Rhizobium leguminosarum 116, an ineffective mutant strain with a defect in iron acquisition, was isolated after nitrosoguanidine mutagenesis of the effective strain 1062. The pop-1 mutation in strain 116 imparted to it a complex phenotype, characteristic of iron deficiency: the accumulation of porphyrins (precursors of hemes) so that colonies emitted a characteristic pinkish-red fluorescence when excited by UV light, reduced levels of cytochromes b and c, and wild-type growth on high-iron media but low or no growth in low-iron broth and on solid media supplemented with the iron scavenger dipyridyl. Several iron(III)-solubilizing agents, such as citrate, hydroxyquinoline, and dihydroxybenzoate, stimulated growth of 116 on low-iron solid medium; anthranilic acid, the R. leguminosarum siderophore, inhibited low-iron growth of 116. The initial rate of 55Fe uptake by suspensions of iron-starved 116 cells was 10-fold less than that of iron-starved wild-type cells. Electron microscopic observations revealed no morphological abnormalities in the small, white nodules induced by 116. Nodule cortical cells were filled with vesicles containing apparently normal bacteroids. No premature degeneration of bacteroids or of plant cell organelles was evident. We mapped pop-1 by R plasmid-mediated conjugation and recombination to the ade-27-rib-2 region of the R. leguminosarum chromosome. No segregation of pop-1 and the symbiotic defect was observed among the recombinants from these crosses. Cosmid pKN1, a pLAFR1 derivative containing a 24-kilobase-pair fragment of R. leguminosarum DNA, conferred on 116 the ability to grow on dipyridyl medium and to fix nitrogen symbiotically. These results indicate that the insert cloned in pKN1 encodes an element of the iron acquisition system of R. leguminosarum that is essential for symbiotic nitrogen fixation.

Protoporphyrin formation in Rhizobium japonicum.

The obligately aerobic soybean root nodule bacterium Rhizobium japonicum produces large amounts of heme (iron protoporphyrin) only under low oxygen tensions, such as exist in the symbiotic root nodule. Aerobically incubated suspensions of both laboratory-cultured and symbiotic bacteria (bacteroids) metabolize delta-aminolevulinic acid to uroporphyrin, coproporphyrin, and protoporphyrin. Under anaerobic conditions, suspensions of laboratory-cultured bacteria form greatly reduced amounts of protoporphyrin from delta-aminolevulinic acid, whereas protoporphyrin formation by bacteroid suspensions is unaffected by anaerobiosis, suggesting that bacteroids form protoporphyrin under anaerobic conditions more readily than do free-living bacteria. Oxygen is the major terminal electron acceptor for coproporphyrinogen oxidation in cell-free extracts of both bacteroids and free-living bacteria. In the absence of oxygen, ATP, NADP, Mg2+, and L-methionine are required for protoporphyrin formation in vitro. In the presence of these supplements, coproporphyrinogenase activity under anaerobic conditions is 5 to 10% of that observed under aerobic conditions. Two mechanisms for coproporphyrinogen oxidation exist in R. japonicum: an oxygen-dependent process and an anaerobic oxidation in which electrons are transferred to NADP. The significance of these findings with regard to heme biosynthesis in the microaerophilic soybean root nodule is discussed.

Nodule-specific host proteins in effective and ineffective root nodules of Pisum sativum.

Nodule-specific root proteins - so called nodulins - were identified in root nodules of pea plants by an immunological assay. Nodulin patterns were examined at different stages of nodule development. About 30 nodulins were detectable during development. Some were preferentially synthesized before nitrogen fixation started, whereas the majority were synthesized concomitantly with leghaemoglobin. Some of the nodulins were located within the peribacteroid membrane. Ineffective Rhizobium strains (a natural nodfix and a pop fix) appeared to be useful in studying the expression of nodulin genes. Synthesis of some nodulins was repressed in ineffective root nodules, indicating that nodulins are essential for the establishment of nitrogen fixation. In both types of ineffective root nodules, leghaemoglobin synthesis was not completely repressed. Low amounts of leghaemoglobin were always detected in young ineffective root nodules whereas in old nodules no leghaemoglobin was present.

Effects of iron deficiency on heme biosynthesis in Rhizobium japonicum.

The effects of iron deficiency on heme biosynthesis in Rhizobium japonicum were examined. Iron-deficient cells had a decreased maximum cell yield and a decreased cytochrome content and excreted protoporphyrin into the growth medium. The activities of the first two enzymes of heme biosynthesis, delta-aminolevulinic acid synthase (EC 2.3.1.37) and delta-aminolevulinic acid dehydrase (EC 4.2.1.24), were diminished in iron-deficient cells, but were returned to normal levels upon addition of iron to the cultures. The addition of iron salts, iron chelators, hemin, or protoporphyrin to cell-free extracts did not affect the activity of these enzymes. The addition of levulinic acid to iron-deficient cultures blocked protoporphyrin excretion and also resulted in high delta-aminolevulinic acid synthase and delta-aminolevulinic acid dehydrase activities. These results suggest the possibility that rhizobial heme biosynthesis in the legume root nodule may be affected by the release of iron from the host plant to the bacteroids.

[Transhepatic endless drainage according to Goetze-Dick in stenoses of the intrahepatic and extrahepatic bile ducts (author's transl)]. / Erfahrungen mit der transhepatischen Endlosdrainage nach Goetze-Dick bei Stenosen der intra- und extrahepatischen Gallenwege.

Results and experiences in 51 transhepatic endless drainage operations according to the method of Goetze-Dick are dealt with, the indication as well as the technique of the operation are discussed in detail. The advantage of this method is based on the fact, that the drain can be easily changed. So patients with inoperable obstructive jaundice can often be given many month of worthwhile life. The extracorporal part of the drain is hardly found to trouble the patients. Also benign intrahepatic obstructions, where no bile duct is left to be anastomized, can be operated on satisfactorily with this method. In spite of the blunt penetration of the liver necessitated by this technique, intra- and postoperative complications are rare. Postoperative care is paramount in avoiding cholangitis.

Stimulation of tetrapyrrole formation in Rhizobium japonicum by restricted aeration.

Cultures of Rhizobium japonicum were grown with vigorous aeration to stationary phase and were then incubated under restricted aeration for several days. Under these "microaerobic" conditions, cellular heme content increased 10-fold, and visible amounts of porphyrins were released into the culture medium. The two predominant porphyrins produced were identified, on the basis of their spectrophotometric and chromatographic properties, as protoporphyrin and coproporphyrin. The cytochrome complement of microaerobic cells partially resembled that of the symbiotic bacteria in that cytochromes alpha-alpha3 were absent and a CO-binding cytochrome 552 was present. During the period of restricted aeration, at the time that the heme content was increasing, there was a similar 10-fold increase in the activities of the first two enzymes of heme biosynthesis, delta-aminolevulinic acid synthase and delta-aminolevulinic acid dehydrase. However, during the same period, the activity of succinyl thiokinase (an enzyme that is required in large amounts whether or not heme is being produced) increased only twofold. These results suggest that reduced oxygen tension may play a role in inducing heme synthesis necessary for leghemoglobin formation and bacterial differentiation in soybean root nodules.

Heme Synthesis in Soybean Root Nodules: I. On the Role of Bacteroid delta-Aminolevulinic Acid Synthase and delta-Aminolevulinic Acid Dehydrase in the Synthesis of the Heme of Leghemoglobin.

During nodulation of soybean (Glycine max) by Rhizobium japonicum, variations in the activities of two enzymes of heme biosynthesis, delta-aminolevulinic acid synthase (ALAS) and delta-aminolevulinic acid dehydrase (ALAD) are described. delta-Aminolevulinic acid synthase activity is found in the bacteroid fraction of nodules, but is not detected in the plant fraction. Bacteroid ALAS activity parallels heme accumulation during nodule development. delta-Aminolevulinic acid dehydrase activity is found in both bacteroid and plant cytosol fractions. Bacteroid ALAD activity is constant or increases during nodulation while plant ALAD activity falls.Bacteroid ALAD activity is found in effective, not in inefficient nodules. Plant ALAD activity is found in both effective and inefficient nodules. Plant ALAD activity falls during development of both types of root nodules.These results support the contention that it is the bacteroid ALAS and ALAD activities, not those of the plant, that are directly involved in formation of leghemoglobin heme, suggesting that the bacteroid may be solely responsible for formation of leghemoglobin heme in the nodule symbiosis.

Calcium Requirement for Indoleacetic Acid-induced Acidification by Avena Coleoptiles.

The ionic specificity of IAA-induced acidification by Avena coleoptiles was studied, using zwitterionic, presumably impermeant buffers. The acidification was almost totally dependent on divalent cations with an order of effectiveness of Ca(2+) >/= Sr(2+) > Mn(2+), Mg(2+); whereas other polyvalent cations tested were ineffective. The Ca(2+) response was IAA-dependent. The CaCl(2) concentration was optimal at 0.3 to 1 mm and inhibitory at higher concentrations. Sr(2+) inhibited Ca(2+)-dependent acidification and monovalent cations such as K(+) did not induce additional acidification in the presence of optimal CaCl(2). These data are consistent with a mechanism for IAA-induced acidification involving a Ca(2+) -H(+) exchange.

Development of chlorophyll and hill activity.

A sensitive luminometer is used to measure directly the low rates of oxygen evolution during greening of etiolated barley (Hordeum vulgare L. var. Wong) leaves. Oxygen evolution is measured in leaf segments infiltrated with p-benzoquinone. When illuminated, these leaves do not produce significant amounts of oxygen until the end of the lag phase of chlorophyll synthesis. Chlorophyll is increased by feeding delta-aminolevulinic acid to leaves in the lag phase, but this does not cause an earlier appearance of photosynthesis. Chloramphenicol, and to a lesser extent cycloheximide, when fed to leaves together with delta-aminolevulinic acid, strongly inhibit the development of oxygen evolution in the light while only slightly inhibiting chlorophyll synthesis. The ability to evolve oxygen develops to only a slight extent in darkness, even in the presence of high levels of chlorophyll.We conclude that the development of photosystem II is limited by the synthesis of proteins in both the cytoplasm and the plastid, not by chlorophyll synthesis. Prolonged illumination is necessary for the development of oxygen evolution.

Controls on chlorophyll synthesis in barley.

In 7- to 10-day-old leaves of etiolated barley (Hordeum vulgare), all of the enzymes that convert delta-aminolevulinic acid to chlorophyll are nonlimiting during the first 6 to 12 hours of illumination, even in the presence of inhibitors of protein synthesis. The limiting activity for chlorophyll synthesis appears to be a protein (or proteins) related to the synthesis of delta-aminolevulinic acid, presumably delta-aminolevulinic acid synthetase. Protein synthesis in both the cytosol and plastids may be required to produce nonlimiting amounts of delta-aminolevulinic acid. The half-life of a limiting protein controlling the synthesis of delta-aminolevulinic acid appears to be about 1(1/2) hours, when determined with inhibitors of protein synthesis. Acceleration of chlorophyll synthesis by light is not inhibited by inhibitors of nucleic acid synthesis, but is inhibited by inhibitors of protein synthesis. A model for control of chlorophyll synthesis is proposed, based on a light-induced activation at the translational level of the synthesis of proteins forming delta-aminolevulinic acid, as well as the short half-life of these proteins. Evidence is presented confirming the idea that the holochrome on which protochlorophyllide is photoreduced to chlorophyllide functions enzymatically.