The role of memory-related gene polymorphisms, KIBRA and CLSTN2, on replicate memory assessment in the elderly.

The role of the CLSTN2 (rs6439886) and KIBRA (rs17070145) SNPs in cognitive impairment was analysed in a 75-76 years old group. Various memory assessment tests were carried out on individuals at baseline and during follow-up investigations, and biallelic genotyping was performed. No influence of the allele status of either SNPs was observed on any memory test. No increased risk of any type of late development, and cognitive impairment was associated with rs6439886 or rs17070145.

The validity of amnestic MCI and non-amnestic MCI at age 75 in the prediction of Alzheimer's dementia and vascular dementia.

BACKGROUND: Clinical subtypes of mild cognitive impairment (MCI) were assigned as potential prodromes to various types of dementia. Amnestic MCI (aMCI) is said to have a high likelihood of progressing to Alzheimer's dementia (AD) and non-amnestic MCI (naMCI) subtypes are assumed to have a higher likelihood of progressing to non-AD dementia. The aim of this study was to investigate the prognostic accuracy of aMCI and naMCI for the development of AD, vascular dementia (VaD), and mixed dementia. METHODS: In this longitudinal study, 487 subjects without dementia (cognitively healthy: n = 387; MCI cases: n = 115) aged 75 years at baseline, who participated in a population-based cohort study (Vienna Transdanube Aging study), were available for analysis. The observation period was 90 months. The diagnoses of the clinical MCI subtypes were made according to common criteria. The outcome (AD, VaD, mixed dementia) was described for both MCI subtypes. Diagnostic values of aMCI and naMCI according to incident AD, VaD, and mixed dementia were determined. RESULTS: AD was the most common type of dementia following both MCI subtypes. Participants with aMCI were more likely to progress to AD than participants with naMCI. The proportion of incident VaD and mixed dementia did not differ concerning the MCI subtypes. The positive predictive value for both MCI subtypes was low (range: 1%-46%), whereas the negative predictive value was high (range: 86%-99%). CONCLUSIONS: The increased risk of clinical MCI subtypes for a particular type of dementia could only be confirmed for aMCI and incident AD.

Risk factors for cerebrovascular and cardiovascular diseases beyond age 75 years.

Globally, cardiovascular diseases (CVDs) are the number one cause of all mortalities. Of these deaths, 7.6 million are due to heart attacks, and 5.7 millions are due to stroke. The Vienna Transdanube Aging Study (VITA), a population-based cohort study, enabled us to evaluate associations between the known major risk factors for cerebrovascular and CVDs and their appearance beyond age 75 years. Using a single birth cohort, age was excluded as confounding factor. In the baseline investigations in the Danube Hospital, 606 individuals took part and were examined completely at baseline. After 60 months, 508 patients were re-examined. Each participant underwent an indepth investigation with the duration of 7 h, including neuropsychological testing, as well as analyses of biochemical, clinical chemical and genetic parameters, and magnetic resonance imaging (MRI) of the brain. In the present study, only a history of cerebral and cardiovascular events at the baseline or smoking was associated significantly with the appearance of CVDs. In a multiple model both risk factors-history of cerebral and cardiovascular events at the baseline (p = 0.0003, OR 2.36, 95% CI 1.49-3.76) and smoking (p = 0.0005, OR 1.57, 95% CI 1.22-2.03)-remained significant. However, the predictive value of this assessment model was low. The rescaled r² of the model was 0.088. A significant correlation was found only between exposure to cigarette smoke or a history of previous CVDs, such as stroke or myocardial infarction. Smoking or earlier CVDs greatly increase the risk for further cerebral and cardiovascular events in persons after 75 years.

VITA study: white matter hyperintensities of vascular and degenerative origin in the elderly.

The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.

Association study of BDNF and CNTF polymorphism to depression in non-demented subjects of the "VITA" study.

BACKGROUND: Neurotrophic factors are known to play an important role in the survival and differentiation of many types of neurons during development. Both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) may act cooperatively in modulating the development and functioning of synapses. Both these neurotrophic factors were intensely investigated with regard to depression without conclusive results. METHODS: We have investigated the possible use of both CNTF null-mutation and BDNF polymorphism C270T as biomarkers for depression in the Vienna Transdanube Aging (VITA) study. The VITA is a prospective community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. RESULTS: We found no association between CNTF null-mutation and BDNF C270T polymorphism to any depressive symptoms after exclusion of demented subjects. CONCLUSION: These results call in question the hypothesis that either BDNF or CNTF can be used as molecular markers for depression or late onset depression in the elderly.

Oxidative stress related markers in the "VITA" and the centenarian projects.

Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Quantitative determination of human protein C. Evaluation of a "fast" functional assay in comparison to a "traditional" functional and an immunological assay.

A fast functional assay for protein C was evaluated and compared with a traditional functional and an enzyme linked immunosorbent assay in parallel for the same plasma samples derived from 43 healthy subjects, 12 patients with severe hepatic dysfunction, and 23 patients under stable oral anticoagulation. By all three test systems significantly lower levels of protein C were obtained in both groups of patients compared with normal subjects (p less than 0.0001). No significant between - assay differences were found in normal subjects and in patients with hepatic dysfunction; by correlation analysis coefficients higher than 0.8 were calculated between the measurements of the three tests. In patients under stable oral anticoagulation, however, the immunologic test yielded higher values than the traditional (p less than 0.05) and, more pronounced, the fast functional assay (p less than 0.0001); no or only borderline significant correlations between the results were found. In these patients protein C levels measured with the traditional functional assay were in the same range as the activity levels of factors II, VII, IX, and X, whereas the fast functional test yielded significantly lower levels. The presented results indicate that very similar protein C levels were obtained with both functional and the immunologic assay except in patients under oral anticoagulation.

Vienna Transdanube Aging "VITA": study design, recruitment strategies and level of participation.

The Vienna Transdanube Aging study "VITA" is a prospective, interdisciplinary cohort-study of all 75-years old inhabitants of the 21. and 22. district of Vienna (n = 1,745), which started in May 2000. The study design is described in this paper for the first time. The main scientific question of the study concerns the prediction of incident dementia in the elderly. The main statistical analysis will compare 8 predictors: episodic memory, verbal fluency, subjective memory complaints, depression, APOE-epsilon4, MAO-B activity in thrombocytes, MRT hippocampal atrophy, and MRT atrophy of the substantia innominata. The whole investigation comprises medical and psychosocial interviews, psychological tests, psychiatric and neurological scales, blood characteristic, genetic factors and cranial magnetic resonance imaging. Various variables will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. The dependent variable of the intended statistical analysis will be the individual's difference between Mini Mental State Examination scores at the two times of investigation. A high level of participation in geriatric epidemiological studies increases the general applicability of results but recruitment procedures must not ignore the individual's right to privacy and integrity. Using a liberal recruitment procedure as recommended by the local ethics commission the level of participation is between 36.7% and 44.3%.

[Improved scintigraphic imaging of the adrenals with 6beta-131I-iodomethyl-cholesterol (author's transl)]. / Verbesserte Nebennierenszintigraphie mit 6beta-131J-Jodmethyl-Cholesterin.

Scintigraphic visualization of the adrenals is greatly improved after substitution of 131I-19-I-Cholesterol by 6beta-131I-Iodomethyl-Cholesterol which was first seen as a radiochemical impurity during the synthesis of 131I-19-Iodocholesterol. The interpretation of the scintigraphic imaging is further improved by application of a cross section through the visualized adrenals. In an animal experiment the radioactivity of the adrenals and to a less degree that of different tissues was found up to four times higher after injection of 6beta-131I-Iodomethyl-Cholesterol than with the applications of 131I-19-Iodocholesterol. The high affinity of the tissue for 6beta-131I-Iodomethyl-Cholesterol results in high radiation exposure of the patients. However, since less activity of 6beta-131I-Iodomethyl-Cholesterol is necessary for visualization of the adrenals the overall radiation is also less than with the application of 131I-Iodocholesterol. Higher stability of the labelled molecule is suggested to be responsible for improved scintigraphic imaging of the adrenals.

[The Danube Hospital in the East Social Medicine Center. Planning, construction and completion]. / Das Donauspital im Sozialmedizinischen Zentrum-Ost. Planung, Errichtung und Inbetriebnahme.

The Danube Hospital is part of a sociomedical center in East Vienna and was conceived to provide medical care for the transdanubian area of the city. In a planned stepwise operation both Depts. of Medicine, the Dept. of Surgery, the Dept. of Traumatology, the Dept. of Gynaecology and Obstetrics, the Dept. of Pediatrics, the Dept. of Pediatric Surgery, the Dept. of Neurology, the Dept. of Physiotherapy, the Dept. of Anaesthesia, the Dept. of Radiology, the Dept. of Laboratory Medicine, the Dept. of Nuclear Medicine, the Dept. of Pathology and Bacteriology, and the hospital pharmacy were opened in April 1992. Both the Dept. of Ear, Nose and Throat and the Dept. of Urology are due to open at the beginning of 1993, while the Dept. of Ophthalmology, the Dept. of Dermatology, the Dept. of Orthopedics, the Dept. of Maxillary Surgery and Dentistry and the Dept. of Neurosurgery will start operation in 1994. With the opening of the Dept. of Psychiatry in 1996 the Danube Hospital will be fully operative. By that time 920 beds, with an additional 59 functional beds (Intensive Care Units, Neonatology, Dialysis Ward, and Admission Unit) will be in operation.

[Localization of adrenal tumors]. / Die Lokalisation von Nebennierentumoren.

The application of newly developed methods to localization of adrenal tumours has improved diagnostic accuracy, yet the challenge still exists. The sensitivity of ultrasound is too low for imaging small adrenal tumours, thus reducing sonography to a screening method. Computed tomography is a fast and sensitive localizing method, even for small tumours, with a low radiation exposure. Endocrine-active tumours with high hormone-secreting activity or displaying a tendency to additional extra-adrenal presentation will generally be best localized by scintigraphic imaging. Sonography and computed tomography as non-invasive methods and invasive puncture of the tumour or of the cyst with consequent cytological examination of the obtained material are most important procedures in the diagnosis of endocrine-inactive adrenal masses.

[The action of insulin on ribonucleic acid metabolism (author's transl)]. / Zur Wirkung von Insulin auf den Ribonukleinsäure-Stoffwechsel

The incorporation of 3H-uridine into liver ribosomes is reduced in alloxan-diabetic rats. This reduction affects mRNA as well as rRNA. Insulin-substitution therapy of diabetic animals restores to normal the incorporation rates of uridine into both mRNA and rRNA. There is a manifest connection between the known reduction of polyribosomes in diabetes mellitus and reduced synthesis of mRNA; moreover, a connection to the reduced production of rRNA seems also to be possible.

[Diabetes mellitus and control of protein biosynthesis in rat liver (author's transl)]. / Zur Eiweisssynthese der Leber beim Diabetes mellitus

Protein synthesis of liver risobosmes is markedly reduced in diabetes mellitus. This finding is well correlated with the protein catabolic state of insulin deficiency in general and with the reduction of protein synthesis by muscle ribosomes in particular. However, with regard to the mechanism of the amino acid incorporation by muscle ribosomes there is indication for an additional participation of transcription in the diabetes-induced reduction of protein synthesis by liver ribosomes. There is support for the hypothesis of an additional effect of diabetes on ribosomal wash proteins and on synthesis of ribosomal ribonucleic acids with consecutive reduction of conformation of ribosomal subunits or binding of ribosomal subunits to template RNA respectively.

[Stability of insulin-bearing liposomes (author's transl)]. / Zur Stabilität von Insulin-tragenden Liposomen.

Stability and integrity of 125I-insulin loaded liposomes are temperature dependent. Only storage close to the phase transition temperature ensures their chromatographic integrity even after nine days. The pH of the buffer also affects the stability of the insulinliposomes. pH changes to 6.0 or 8.5 alter the elution pattern of the liposomes. The sensitivity of insulinliposomes to temperature and pH is of importance with regard to their in vivo application.

[Oral administration of insulin by means of liposomes in animal experiments (author's transl)]. / Zur peroralen Verabreichung von Insulin mittels Liposomen im Tierversuch.

Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved.

[Anaemia with medullary myeloblastosis (author's transl)]. / Refraktäre Anämie mit medullärer Myeloblastose.

A case of refractory anaemia with medullary myeloblastosis (RAMM) is described. RAMM is a very rare disease and its relationship to aplastic anaemia and smouldering leukaemia is not clearly established. The diagnosis is confirmed by evaluation of the bone-marrow aspirate and ferrokinetic studies which demonstrate ineffective erythropoiesis. The disease is combined with leucopenia, thrombocytopenia and a hyperplastic bone-marrow. Our patient was monitored for 18 months, during which time her haematological findings remained stable. Since transformation into acute leukaemia occurs in about 25% of the cases, a bone-marrow culture study was performed in order to determine such a leukaemic transformation which is not detectable on examination by the light microscope. Culture studies are discussed along with some prognostic, therapeutic and pathophysiological problems of RAMM.

Bleomycin as carrier substance for 99m-Technetium in tumour diagnosis (author's transl). / Bleomycin als Trägersubstanz für 99m-Technetium in der Tumordiagnostik

99m-Tc-Bleomycin is a promising tool for scintigraphic imaging of some types of malignant tumours. The rapid decay of 99m-Tc, together with a high affinity of bleomycin for certain histologically-defined tumours recommends its use in humans. Moreover, by using high specific activities of bleomycin, no toxic effects are to be expected. At 00-C, the chelate of 99m-Tc and bleomycin is stable and its storage or transport are recommended at this temperature. Following the i.v. injection of rats with 99m-Tc-bleomycin, a high specific activity is found in the liver, spleen, lungs and skin. In view of its excretion by the kidneys an extremely high activity is found in the urogenital system. Scintigraphic imaging of lymph nodes in a case of Hodgkin's disease, of a embryonal carcinoma, of a thyroid carcinoma, of an astrocytoma and of a solid carcinoma was obtained in patients investigated by this method.

[The clinical relevance of scintigraphic adrenal imaging (author's transl)]. / Klinische Erfahrungen mit der szintigraphischen Nebennierendarstellung

Labelled steroid precursors have been found to be valuable in scintigraphic imaging of localized adrenal disease or even in adrenal hyperplasia. Scanning procedures are non-invasive diagnostic methods and, in the case of the adrenals the images reflect anatomical as well as functional changes in the organs, constituting an advantage over angiographic methods. However, careful preparation of the patient, sophisticated technical prerequisites and a case-oriented programme of the procedure favouring either dexamethasone suppression, comparsion with phantom measurements adrenal profiles and/or multichannel analysis are necessary for the attainment of optimum results on scintigraphy.

[The influence of somatostatin on serum gastrin concentrations in patients after total duodenopancreatectomy (author's transl)]. / Die Wirkung von Somatostatin auf die Serumgastrinkonzentration bei Patienten nach totaler Duodenopankreatektomie

Serum gastrin concentrations were measured in insulin-dependent diabetics and in patients who had undergone total duodenopancreatectomy and gastrectomy. Administration of somatostatin markedly inhibited gastrin release in the diabetic patients with an intact gastrointestinal tract. This inhibitory effect of somatostatin, however, is not detectable in the group of operated patients, who display basically low plasma gastrin levels. A marked increase in the plasma gastrin level after withdrawal of somatostatin was observed in patients with a normal gastrointestinal tract. This rebound effect was only slight in the operated patients.

[ Somatostatin in insulin-dependent diabetics and in pancreatectomized patients (author's transl)]. / Zur Wirkung von Somatostatin bei insulinpflichtigen Diabetikern und bei pankreatektomierten Patienten

The inhibitory effect of somatostatin on the secretion of glucagon permits the examination of the effect of glucagon on some metabolic parameters in the insulin-dependent diabetic patient. The results obtained in 5 insulin-dependent diabetics and in 4 pancreatectomized patients revealed an inhibitory effect of somatostatin on blood glucose in the juvenile-type diabetics, but failed to show this influence of somatostatin in the pancreatectomized patients. These observations indicate a participation of glucagon in the generation of hyperglycaemia in diabetes mellitus. However, the failure of somatostatin to influence the blood glucose level in pancreatectomized patients contrasts with the results obtained in dogs and emphasizes the difficulty and pit falls in the application of animal experiments with somatostatin to humans.