[Does an association between increased homocystein levels and cognitive dysfunction also exist in multimorbid geriatric patients]. / Besteht auch bei multimorbiden geriatrischen Patienten ein Zusammenhang zwischen erhöhten Homocysteinspiegeln und kognitiven Defiziten?

BACKGROUND: Total blood homocysteine (Hcys) and folate have been investigated in association with cognitive dysfunction (CD) in healthy but not in multimorbid elderly patients. We hypothesized that total Hcys and folate are adequate markers to identify multimorbid elderly patients with CD. METHODS: According to the Short Performance Cognitive Test (SKT) CD was determined in a cross-sectional study with 189 (131 f/58 m) multimorbid elderly patients with a mean age of 78.6 +/- 7.3 yrs. Besides the analyses of biochemical parameters (Hcys, folate, vitamin B(12), hemogram) nutritional status (BMI, Mini Nutritional Assessment) as well as activities of daily living were assessed. Daily nutritional intake was measured with a 3-day nutrition diary. For analysis, we used the nutritional software program DGE-PC professional. RESULTS: According to SKT 25.4% showed no cerebral cognitive dysfunction, 21.2% had a suspicion about incipient cognitive dysfunction, 12.7% showed mild, 9.0% moderate, 31.7% of patients severe cognitive deficits. Median plasma Hcys was about 20% elevated in multimorbid elderly patients independent of CD. Serum folate and vitamin B(12) levels were within range, though dietary folate intake (97 [80-128] microg/d) was reduced about 75% (recommendation 400 microg/d). Significant correlations between vitamin intake and plasma/serum levels of Hcys, folate and vitamin B(12) were not present. We did not find significant differences between SKT groups of nutritional status, activities of daily living, index of diseases, medications, or selected biochemical parameters. CONCLUSION: We analysed elevated serum Hcys levels in multimorbid elderly patients with normal plasma folate and vitamin B(12) concentration and CD. Plasma Hcys or serum folate did not appear as an important biological risk factor on CD in multimorbid elderly patients.

[Subjective perception of and coping with dementia in its early stages. A qualitative interview study with people with dementia and their relatives - SUWADEM]. / Subjektive Wahrnehmung und Bewältigung der Demenz im Frühstadium - SUWADEM: Eine qualitative Interviewstudie mit Betroffenen und Angehörigen.

The study SUWADEM has completed the long overdue transition from objective to subjective research in the field of dementia in Germany. The perception and coping processes are reconstructed on the basis of 25 interviews with people with dementia (Pwids) and their family members. Data collection and analysis were conducted on principle of a qualitative research method, the "Grounded Theory". The subjective experience of dementia was presented in a biopsycho-social perspective. On the basis of the identified subjective ageing and disease theories, Pwids evaluate their perceived cognitive and functional deficits. According to the evaluation outcome the emotional distress varies. The lack of insight into the disease (anosognosia) in the early stage is mainly due to psychological (e.g. internalised stereotypes concerning old age) and social factors (e.g. undifferentiated subjective disease theories of person in authority). Within the framework of the disease coping process, anosognosia is a function of different forms of self-protection: (1) The regulation of emotions and the stabilisation of the sense of self-worth, (2) resistance to stigmatisation, (3) defence of one's own autonomy. The results indicate the importance of public relations work, which is intended to raise public awareness of the early stages of dementia. In addition Pwids have to be active partners in dementia research and in the development of support structures. Finally the development and evaluation of person-centered single- and group-interventions is absolutely necessary.

[On disclosing a diagnosis of dementia]. / Die Patientenaufklärung bei Demenz.

Disclosing a diagnosis of dementia to the patient has become a scientific topic only in the last decade. This review gives an up-to-date account of ongoing research. After an introductory discussion of the pros and cons, the unsatisfactory situation of disclosure in the European Union is analysed. Afterwards, the wish of being told a diagnosis of dementia among healthy old people, people with dementia and their relatives is described. The first empirical studies about coping with the diagnosis are presented. Suggestions of new directions in coping research are made. Finally, recommendations for communicating the diagnosis to the patient and the family are given.

[Agreement on the Barthel Index. A rapid analysis of other and self-assessment in elderly stroke patients]. / Beurteilungsübereinstimmung beim Barthel-Index. Eine Rasch-Analyse der Fremd- und Selbstbeurteilungen älterer Schlaganfall-Patienten.

The relationship between staff and patient ratings of activity restrictions (Barthel Index, BI) was investigated in 120 elderly stroke patients (on average 78 years old) using the Rasch model and the rating scale analysis. In addition, the relationship between the rated activity restrictions and measures from the Geriatric Assessment was analyzed. We found good patient-staff agreement (r = 0.90) with the poorest agreement in the item "bathing" of the BI. There was also a highly significant correlation between staff and patient ratings and the Tinetti Gait and Balance Scales (r = 0.72 and r = 0.76, respectively). Correlations between other measures of the Geriatric Assessment and the rated activity restrictions were low explaining less than 8% of variance. Our findings merit the use of patient ratings of activity restrictions in stroke outcome research. However, self-ratings of activity restrictions were measured by an unstructured interview and it cannot be ruled out that this method had an influence on the correlation between self-rating and staff rating.

Effect of ivermectin in Dipetalonema viteae and Litomosoides carinii infections of Mastomys natalensis.

In D. viteae infected M. natalensis oral or subcutaneous (s.c.) treatment with ivermectin on 5 consecutive days with at least 0.05 mg/kg and single dose treatment with 0.1 mg/kg caused a 100% reduction of microfilaraemia throughout the investigation period of 42 days. Using lower doses (lowest dose used 5 X 0.003 mg/kg) animals were free from circulating microfilariae at least until day 7. The drug was active against adult worms. Treatment with doses of 5 X 0.2 mg/kg and above resulted in 81-93% and 38-83% reductions of male and female worms, respectively. Lower doses caused inconsistent macrofilaricidal effects but mainly male worms were affected. After treatment with 5 X 3.25 mg/kg and above increased rates of pathologically altered intrauterine stages were found in surviving female worms. After treatment of L. carinii infected Mastomys with doses of at least 5 X 1.5 mg/kg animals remained amicrofilaraemic until autopsy on day 42 and in case of lower doses (lowest dose used 5 X 0.006 mg/kg) at least until day 7. After single dose treatment (s.c.) with 0.2 mg/kg and above animals were free from microfilariae in the blood throughout the observation period. Single dose treatment with 0.05 and 0.0125 mg/kg removed all microfilariae from the blood until 8 and 48 hours, respectively but microfilariae occurred in the blood again after 14 days. Ivermectin did not affect the numbers of adult L. carinii but female worms isolated 42 days after treatment with 5 X 0.78 mg/kg and above were free from motile, normally shaped microfilariae and contained increased rates of pathologically altered embryonic stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Reaginic and homocytotropic IgG antibody response of Mastomys natalensis in experimental infections of filarial parasites (Litomosoides carinii, Dipetalonema viteae, Brugia malayi, B. pahangi).

Reaginic and homocytotropic IgG antibodies in sera using passive cutaneous anaphylaxis (PCA) test and antigen from Litomosoides carinii were followed in Mastomys natalensis, infected with L. carinii, Dipetalonema viteae, Brugia malayi or B. pahangi. Groups of animals with infections of various ages so as to cover a total infection period of up to 300 to 420 days post-infection (p.i.), depending on the species of parasites, were bled at 1- to 3-week intervals over periods of 50-112 days. In addition, intradermal tests were performed on animals infected with L. carinii to detect immediate type hypersensitivity. Reaginic antibodies were usually first detected in the 3rd week after infection. Thereafter, a marked increase of PCA titres was observed in the 4th week p.i. leading to maximum titres 4 weeks after infection with D. viteae and B. pahangi and 6 weeks after B. malayi infection. Mean maximum titres were between 1:40 and 1:160. Following the peak response, titres decreased markedly until the beginning of patency in infections with D. viteae, B. malayi and B. pahangi whereas a constant course was observed at this time in animals infected with L. carinii. A further rise in PCA titres occurred in all infections around the beginning of patency, resulting in maximum reagin levels in L. carinii infections (mean titre 1:80) and moderate titres in the other infections. During early patency there was an inverse relationship between microfilaraemia density and levels of reaginic antibodies. However, in the phase of decreasing parasitaemia in L. carinii infected animals, microfilariae counts and PCA titres were directly correlated. Homocytotropic IgG antibodies showed relatively constant PCA titres of about 1:20 in L. carinii infected Mastomys throughout the observation period. In D. viteae infections they were demonstrated at 30 days p.i., reaching titres of about 1:40. B. malayi infected animals showed a maximum titre of 1:40 40 days p.i.. Thereafter, titres decreased continuously and homocytotropic IgG antibodies were absent at 110 days p.i.. High titres were observed at day 150 but thereafter sera were negative. B. pahangi infected animals showed moderate titres (1:5) 35 days p.i.. Thereafter, antibodies were found at low titres until 115 days p.i.. Intradermal reactions in L. carinii infected animals generally increased in size from 30-60 but decreased when microfilariae appeared in the blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Filarial infections of Mastomys natalensis and their relevance for experimental chemotherapy.

Experimental filarial infections of Mastomys natalensis, strain GRA Giessen, with Litomosoides carinii, Dipetalonema viteae, Brugia malayi (subperiodic), and Brugia pahangi were compared. Mean prepatent periods of 52, 57, 107, and 73 days p.i. were observed after subcutaneous inoculation of 40, 50, 85, and 70 infective larvae of L. carinii, D. viteae, B. malayi, and B. pahangi, respectively, in the neck region. All of the L. Carinii, D. viteae, and B. pahangi infected Mastomys showed a regularly detectable microfilaraemia. In B. malayi infections 95.5% of the animals developed parasitaemias, when the larvae had been inoculated in the neck region, whereas after groin infections only in 66.7% of the animals became patient. For both Brugia species, infections in the groin resulted in considerably lower microfilarial levels. Maximum microfilariae densities could be detected at day 120 (L. carinii) and at day 1980 (D. viteae) p.i. In the case of Brugia neck infections, the microfilarial levels increased usually until the end of the observation period, 300-350 days p.i. Worm recovery rates were 63% (L. carinii), 20.6% (D. viteae), 21.1% (B. malayi), and 31.4% (B. pahangi) of the inoculated larvae. When third stage larvae of Brugia species were inoculated in the neck region, adults of B. malayi and B. pahangi were isolated predominantly from the heart of lungs (84.4 and 78.5%, respectively). Only 12.3% of B. pahangi parasites were found in the testes; 3.4% and 18.1% were localized in the lymphatics. After inoculation of infective larvae in the groin more worms could be recovered in the testes and lymphatics, i.e. 23.4% and 14.9% (B. malayi) or 19.1% and 45.2% (B.pahangi), respectively. The results are discussed under the aspect of chemotherapeutic investigations for the evaluation of microfilaricidal, macrofilaricidal or chemoprophylactic compounds. It is concluded, that Mastomys natalensis, an animal with a broad spectrum of susceptibility for filarial infections, can be used as an alternative experimental model system, similar to that of the jird.

[Immunization against Capillaria hepatica: the effects of primary infections, x-irradiated stages, non-embryonated eggs, and soluble egg extracts (author's transl)]. / Immunisierung gegen Capillaria hepatica: Die Wirkung von Erstinfektionen, röntgenattenuierten Stadien, nicht embryonierten Eiern und löslichen Eiextrakten.

The influence of primary infections with embryonated infective eggs or with X-irradiated infective eggs, and of non-embryonated eggs, and egg homogenate extracts on challenge infections with Capillaria hepatica was investigated. The worm reproductivity was significantly suppressed in a sublethal challenge infection given 11 days after a primary infection of Mastomys natalensis with 50, 150, 400, and 800 eggs per animal. The administration of 600 X-irradiated (2.2 Krd) embryonated eggs 36 days before challenge as well as an intraperitoneal injection of non-embryonated eggs 12, 10, 8, 6, 4, and 2 days before challenge (simulating the egg production of a normal infection) also reduced significantly the egg production of a weak (50 eggs/ animal) infection. No effect was observed on a moderate challenge (300 eggs/animal). The effect was not markedly enhanced by the repeated administration of X-irradiated eggs or by the combination of X-irradiated infective eggs and non-embryonated eggs. Immunization of mice with soluble egg extracts resulted in significant reduction of egg production determined 60 days after challenge. Two hundred and thirty eggs of C. hepatica/g body weight proved to be a lethal infection dose for M. natalensis. The animals died between 20 and 35 days after infection. After single infections with 50, 150, 400, or 800 eggs per animal the mortality of Mastomys challenged 36 or 52 days later was reduced to 0--30%. Using X-irradiated embryonated eggs for immunization only repeated administration led to protection in 70 to 80% of the animals. About 40% of the animals could be protected by the intraperitoneal injection of non-embryonated eggs. If death occurred it was delayed. The combination of X-irradiated stages and eggs did not enhance the protection.

The cellular responses in Marisa cornaurietis experimentally infected with Angiostrongylus cantonensis.

The cellular responses in the poorly susceptible ampullariid snail Marisa cornaurietis to Angiostrongylus cantonensis, during a period of 40 days, involved focal and generalized proliferative reactions. The focal reactions appeared around all larvae as accumulations of variable numbers of amoebocytes at 24 h after infection in the loose connective tissues and somewhat later in the dense tissues. This cellular infiltration intensified gradually with time leading to the encapsulation of the parasite. At 18 days after infection a central zone formed mainly of hypertrophic, granular, highly acidophilic amoebocytes and a peripheral zone of fibrous appearance were conspicuous in most capsules. The generalized proliferative reaction appeared at about day 4 after infection as leucocytosis in the vascular system of the snail and in the connective tissue. At 25 days after infection many leucocytes which are markedly hypertrophic, highly eosinophilic, and densely granulated were found in the vascular system. These cells were spread in the connective tissues and contributed to the formation of the capsules at 40 days after infection. The sources of amoebocytes appear to be mainly several hyperactive areas in the loose connective tissue and in the lung, some active foci in the body wall at the head region, and also in an amoebocyte-producing organ which lies in the roof of the lung.

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 8. The action of furazolidone on adult worms and microfilariae.

After oral administration of furazolidone in doses of 5 x 50 mg/kg and 1 x 100 mg/kg body weight to Litomosoides carinii--infected Mastomys natalensis microfilaraemia decreased continuously and was reduced by more than 98% 42 days after start of treatment. After the 5-day treatment all adult female and male worms were found dead and encapsulated within 2 weeks, whereas after the single dose 100% of the female parasites were encapsulated 28 days after treatment. In untreated animals quantiative examinations of the intrauterine stages showed an average number of 500 x 103 embryos per adult female worm. Following the 5-day treatment the number of embryos per female parasite was reduced after 42 days to 12.5 x 103, and after the single treatment to 26.9 x 103. By classification into 5 different stages (2- and 4-cell stages, Morula stage, "Horse-shoe" stage, "Ring" and "Brezel" stages, and intruterine microfilariae) an embryogram showed a continuous increase in pathologically-altered embryos during the whole observation period. The 2- and 4-cell stages suffered the most damaged. By 16 days after the end of the 5-day treatment and by 28 days after the single treatment all embryonic stages in the uteri were found to be pathologically altered. Furazolidone possessess high macrofilaricidal activity together with a considerable adverse effect on embryognesis and some delayed effect on microfilaraemia.

CELISA (complement-enzyme linked immuno sorbent assay) a new method for the estimation of complement fixing antibodies; its use for Chagas' disease.

A description is given of a new method for the estimation of complement fixing antibodies. This is a modification of the Enzyme Linked Immuno Sorbent Assay (ELISA) to a Complement-Enzyme Linked Immuno Sorbent Assay (CILISA) using an anti-C3 conjugate. The method is independent of the haemolytic system. To test the sensitivity of CELISA, comparative studies were carried out with the Haemolytic Complement Fixation Test (CFT), indirect haemagglutination test and ELISA with sera from patients with Chagas' Disease. The results with CELISA showed significant correlations with CFT titers whereas no correlations were observed with the other serological tests.

On Dipetalonema viteae infection of Mastomys natalensis.

Experimental infections were carried out with the tissue-dwelling filaria Dipetalonema viteae using the argasid tick Ornithodorus moubata as the intermediate and the multimammate rat Mastomys natalensis (Strain GRA Giessen) as the final host. The optimum infective dose was found to be 50 third-stage larvae, which produced patent infections and the recovery rates of adult parasites were 47.6 and 26.4% of the inoculated larvae 140 and 189 days after infection, respectively. After an average prepatent period of 57 days, the microfilaraemia increased progressively and reached relatively low maximum values about 192 days after infection. These maximum values were followed by rapid decrease of microfilaraemia, but microfilariae were still detectable at 261 days post infection. Following the subcutaneous injection of infected animals with dexamethasone in single doses each of 1, 10 or 20 mg/kg body weight 30 minutes before blood puncture, a dose-dependent increase in the microfilarial counts in the circulating blood was observed, this reaching maximum values between 120 and 160 days after infection. Repeated administration of single doses of 10 mg/kg dexamethasone revealed an uniform but temporary increase in the microfilaraemia but this was not associated with any alterations in the reproductive organs of adult female parasites. No correlation could be found between the number of microfilariae in the circulating blood and the number of adult worms recovered from the subcutaneous connective tissue. At necropsy 300 days after infection living female parasites could not be found any more.

The efficacy of anthelmintics against third stage larvae of Ancylostoma caninum in Mastomys natalensis.

Investigations have been carried out on the multimammate rat (Mastomys natalensis), orally infected with 1000 third stage larvae of Ancylostoma caninum per animal, to evaluate the larvicidal efficacy of anthelmintics in this paratenic host. The oral or subcutaneous administration of 19 anthelmintics and filaricides revealed good activity for levamisole, cambendazole, and mebendazole against 15-day-old Ancylostoma larvae which were located in the muscular tissue. Similarly, good results were obtained with levamisole and cambendazole against the migrating third stage larvae, by treatment two to six days after infection. The benzimidazole derivatives, thiabendazole, oxibendazole, parbendazole, and fenbendazole showed marked activity only at high dosage rates. The anthelmintics methyridine, amoscanate, pyrantel tartrate, morantel tartrate; the microfilaricidal organophosphates dichlorvos, fenthion, and haloxon; as well as the micro- or macrofilaricidal drugs diethylcarbamazine, nitrofurantoin, nifurtimox, suramin sodium, and thiacetarsamide sodium failed to show larvicidal activity even in high dosages. The average larval recovery rate after oral infection with 1000 third stage larvae, in untreated control animals, was 14.85%.

[Alteration of enzyme activities in serum of Eimeria stiedai infected rabbits (author's transl)]. / Veränderungen der Enzymaktivitäten im Serum bei Eimeria stiedai infizierten Kaninchen.

In experimental investigations on Eimeria stiedai infected rabbits, serum enzymatic studies have been carried out in correlation with the examination of parasitological and pathological parameters. The rabbits were orally infected with a single dose of either 100,000 or 250,000 sporulated oocysts. Increase of the activity of the sorbit dehydrogenase (SDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GlDH) could be found first between 3 and 10 days after infection indicating the beginning of the acute phase of liver coccidiosis. The increase of the conjugated bilirubin and of the gamma-glutamyl-transferase (gamma-GT) could be found not earlier than 10 days after infection and is to be explained as sign of disturbed efficiency of excretion. The various investigated parameters reached their peak of alteration about the end of the prepatent period and at the beginning of patency between 14 and 21 days after infection. The results emphasize the value and usefulness of serum enzymes, particularly the glutamate dehydrogenase (GlDH) and the gamma-glutamyl-transferase (gamma-GT) with about 30fold activity, as indicators in the course of Eimeria stiedai infection of rabbits. The enzymes returned to physiological values at the end of the experiment, 42 days after infection. Significant differences could not be detected within the infected groups. The activities of the alkaline phosphatase (AP), leucine aminopeptidase (LAP), choline esterase (ChE), lactate dehydrogenase (LDH) and isoenzym 1 (alpha-HBDH) showed only slight alterations and proved to be no significant parameters for the pathophysiological evaluation of the liver coccidiosis.

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 7. Filaricidal activity of furazolidone.

Investigations were carried out on the filaricidal activity of furazolidone against Litomosoides carinii infection in Mastomys natalensis. Oral administration of the drug in daily doses of 25, 50, 75, and 150 mg/kg body weight on 5 consecutive days revealed respectively 96,4, 99,3 and, with the two later doses, 100% reduction of macrofilariae in the pleural cavities, and produced a continuing dose-dependant decrease of microfilaraemia in the circulating blood. After oral doses of 5 x 50 mg/kg, all the adult parasites were killed within two weeks of the start of treatment and were found encapsulated in fibrinous masses in the pleural cavities. Deformed and degenerated embryonic stages could be seen in female worms as early as 3 days after the end of treatment. Furazolidone possesses a considerable chemotherapeutic index.