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Biomedical subjects

J Eckert

Publications and source records attributed to J Eckert.

At least 19 recordsLinked to original sources

[Swiss study of chemotherapy of alveolar echinococcosis--review of a 20-year clinical research project].

Alveolar echinococcosis (A. E.), caused by Echinococcus multilocularis, behaves biologically like a malignant tumour of the liver which is best treated by radical surgery. However, radical surgery can be performed only in about 20-30% of A. E. cases. The efficacy of chemotherapy with benzimidazole derivatives for inoperable cases is debated. The results of a prospective Swiss chemotherapy trial, which started in 1976, are reviewed. In the last 20 years a total of 110 patients has been included in our protocol and 74 of these patients had inoperable or palliatively operated A. E. (average observation time 12.8 years). The efficacy of long-term chemotherapy was documented by increase of 10-year survival compared to historical (untreated) A. E. cases (80 vs 6%) and by reduction or stabilisation of the liver lesions in 83% of cases during long-term chemotherapy. Several relevant problems remain to be clarified, e.g. optimal duration of chemotherapy, the controversy as to whether chemotherapy is parasitostatic or parasitocidal, the establishment of reliable routine methods for short-term assessment of therapeutic efficacy, and comparative studies between mebendazole and albendazole. Furthermore, additional studies are necessary in collaboration with basic science, for example on the impact of the increasing fox population, with invasion of large agglomerations, on infection risk in the Swiss population, and the importance of individual immune competence for susceptibility or resistance to A. E.

Albendazole

Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms.

BACKGROUND: Catatonia was first described by Kahlbaum as a psychomotor disease with motor, behavioral, and affective symptoms. In keeping with this concept, we developed a rating scale for catatonia (Northoff Catatonia Scale [NCS]) with three different categories of symptoms (i.e., motor, behavioral, affective). Furthermore, the question of the relationship among catatonic symptoms, extrapyramidal motor symptoms, and neuroleptics was addressed in the present study. METHOD: 34 acute catatonic patients and 68 age-, sex-, diagnosis-, and medication-matched psychiatric control subjects were investigated on days 0, 1, 3, 7, and 21 with the NCS, with other already validated catatonia rating scales by Rosebush, Bush (BFCRS), and Rogers (MRS), as well as with scales for hypokinetic (SEPS) and dyskinetic (AIMS) extrapyramidal motor features. Validity and reliability of the new scale, factor analysis, correlational analysis, and differences between catatonic patients and psychiatric control subjects were statistically calculated. RESULTS: NCS showed high validity (i.e., significant positive correlations [p <0.0001] with the other scales, significant differences between catatonic and control subjects), high intra-and interrater reliabilities (r = 0.80-0.96), and high affective subscores. Factor analysis revealed four factors best characterized as affective, hypoactive, hyperactive, and behavioral. Catatonic scores in NCS correlated significantly with AIMS on day 0 and SEPS on days 7 and 21. There were no significant differences in catatonic (i.e., NCS, MRS, BFCRS) and extrapyramidal (i.e., AIMS, SEPS) scores between neuroleptically treated and untreated catatonic subjects. CONCLUSIONS: The following conclusions were drawn: (1) the NCS has to be considered as a valid and reliable rating instrument for catatonia; (2) catatonia can be characterized by psychomotor symptoms encompassing motor, affective, and behavioral alterations; and (3) extrapyramidal hyperkinesias like dyskinesias are apparently closely related to catatonic symptoms which, in general, seem to be relatively independent of previous neuroleptic medication.

Acute Disease

Alveolar echinococcosis in humans: the current situation in Central Europe and the need for countermeasures.

Alveolar echinococcosis (AE) in humans is caused by a larval stage (metacestode) of Echinococcus multilocularis, which exhibits a tumor-like growth, initially in the liver, with the potential to induce serious disease. At the end of the 1980s, E. multilocularis was known to occur in four countries of Central Europe, but has now been identified in ten countries. Red foxes are the principal definitive hosts of E. multilocularis and sources of human infection, but dogs and cats can also be infected. Growing populations of foxes and their increasing immigration to urban areas are new risk factors. Human AE is rare but its potential high fatality rate, considerable costs of treatment and the persisting infection risk should be reasons for health authorities in European countries to establish coordinated systems of surveillance and risk assessment in combination with measures to reduce morbidity and mortality of AE in the human population. Here, J. Eckert and P. Deplazes outline the current epidemiological situation in Central Europe, and discuss options for surveillance, prevention and control.

Animals

Reduced activation and altered laterality in two neuroleptic-naive catatonic patients during a motor task in functional MRI.

BACKGROUND: Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). METHODS: Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). RESULTS: Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. CONCLUSIONS: In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Acute Disease

Echinococcus multilocularis coproantigen detection by enzyme-linked immunosorbent assay in fox, dog, and cat populations.

A sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Echinococcus multilocularis coproantigens (EM-ELISA) was developed with polyclonal rabbit (solid phase) and chicken egg (catching) antibodies that were directed against E. multilocularis coproantigens and somatic worm antigens, respectively. In experimentally infected dogs and cats, coproantigens were first detectable 6-17 days postinfection (PI) in samples of 8 dogs (worm burdens at necropsy: 6,330-43,200) and from 11 days PI onward in samples of 5 cats infected with 20-6,833 worms. After anthelmintic treatment of 4 dogs and 5 cats at day 20 PI, coproantigen excretion disappeared within 3-5 days. The sensitivity of the ELISA was 83.6% in 55 foxes infected with 4-60,000 E. multilocularis, but reached 93.3% in the 45 foxes harboring more than 20 worms. The EM-ELISA was used in surveys of "normal" dog and cat populations in Switzerland. Among 660 dogs and 263 cats, 5 dogs and 2 cats exhibited a positive reaction. In 2 of these dogs (0.30%) and 1 cat (0.38%), intestinal E. multilocularis infections were confirmed by necropsy, polymerase chain reaction PCR, or both. The specificites of the ELISA in these groups were found to be 99.5% and 99.6%, respectively, if positive ELISA results that could not be confirmed by other methods were classified as "false positive" reactions.

Animals

Canine leishmaniosis in Cyprus due to Leishmania infantum MON 1.

During a serological survey in 1996, a total of 601 dogs (group I) distributed all over the government controlled southern area of Cyprus was examined using an enzyme-linked immunosorbent assay (ELISA) for the presence of specific antibodies directed against soluble antigens of promastigote stages of Leishmania infantum. The overall seroprevalence rate in this group was 1.7%. A second group (group II) of dogs was selected from regions where seropositive dogs where determined within the first group. In group II specific anti-Leishmania antibodies could be detected in 30 of 301 dogs investigated (10%). The highest seroprevalence rates were found in the regions of Agios Georgios (26.2%) and Limnatis (12.2%). Ten parasite isolates from ten dogs (six with typical symptoms of canine leishmaniosis and four without symptoms) originating from five locations could be characterised by zymodeme analysis. All ten isolates were identified as L. infantum zymodeme MON 1.

Animals

A detailed analysis of pronucleus development in bovine zygotes in vitro: cell-cycle chronology and ultrastructure.

The aim of the present experiment was to analyze the chronology of pronucleus development and DNA synthesis, as well as the ultrastructure of intranuclear bodies, in bovine zygotes produced in vitro. Bovine oocytes were matured and fertilized in vitro, and sperm penetration and pronucleus development were examined. DNA synthesis was investigated by sequential incubation with [3H]- and [14C]thymidine followed by autoradiography on semithin sections. Ultrathin sections for transmission electron microscopy were prepared from the same zygotes. Sperm penetration was noted for the first time at 4 hr after in vitro insemination and reached a maximum at 6 hr. Pronucleus formation was initiated at 4 hr, and up to at least 11 hr the maternal pronucleus was more developed than its paternal counterpart. DNA synthesis was initiated at 14-15 hr, and the S-phase lasted for 8-10 hr. The most prominent ultrastructural entities of the pronuclei were the nucleolus precursor bodies (NPBs). During the S- and G2-phases, the NPBs spatially associated with clusters of interchromatin-like granules. The two components were firmly attached to each other by an electron-dense reticulum. During the late G2-phase, the NPBs were apparently detached from the interchromatin-like granules and the electron-dense reticulum again. The interaction between the intranuclear bodies and granules appears to be comparable with the situation previously described for in vivo-produced bovine zygotes (J Laurincík et al., Mol Reprod Dev 43:62-69, 1996), except for the lack of vacuolization of the NPBs during the S-phase in vitro.

Animals

Long-term mebendazole therapy may be parasitocidal in alveolar echinococcosis.

Long-term chemotherapy of human alveolar echinococcosis with benzimidazole compounds (mebendazole, albendazole) has been shown to be primarily parasitostatic, but its curative (parasitocidal) efficacy is debated. This article reports on a 67-year-old male patient with non-resectable alveolar echinococcosis of the liver who had been continuously treated for 13 years with mebendazole (approximately 45-48 mg/kg body weight per day) and who was closely monitored according to a specific protocol. At the age of 80 years the patient died of oesophageal variceal bleeding. During treatment the hepatic lesion had decreased markedly in size in association with progression of perifocal calcification. At autopsy, a well-demarcated, necrotic, partially calcified, parasite-induced lesion of the right liver lobe and secondary biliary cirrhosis were found. Remnants of parasite tissue obtained from the periphery of the lesion showed a small-cystic structure, but it was not viable, as evidenced by transplantation of tissue blocks to rodents. The case is suggestive for a parasitocidal efficacy of mebendazole treatment carried out for 13 years, and is discussed in context with conflicting literature data.

Aged

Exogenous protein affects developmental competence and metabolic activity of bovine pre-implantation embryos in vitro.

The role of exogenous protein during bovine pre-implantation embryo development in two in vitro production systems was investigated. Morphological development, survival after vitrification and metabolic activity before and after vitrification were recorded in blastocysts generated in vitro in synthetic oviduct fluid (SOF) medium in the presence of either bovine serum albumin (BSA) or polyvinyl-alcohol (PVA). Metabolic activity was determined by measuring oxygen consumption, glucose and pyruvate uptake as well as lactate production. Development to blastocysts and survival after vitrification were reduced significantly in medium lacking protein. Of the metabolic parameters measured, only pyruvate uptake was increased significantly in embryos cultured in medium supplemented with PVA. Whereas in BSA-supplemented medium pyruvate uptake was correlated with lactate production, in PVA-supplemented medium glucose uptake was correlated with lactate production. Lactate production increased significantly after vitrification as compared with fresh embryos. Thus, exogenously added protein significantly alters oxidative metabolism. In medium lacking protein, the additional pyruvate may be used for the maintenance of intracellular amino acid pools. Vitrification appears to alter glycolytic metabolic profiles indicating a stress-response. In conclusion, the perturbed metabolism corresponding to reduced developmental capacity of embryos produced under protein-free conditions emphasizes the ambiguity between maximum development, technical and hygienic requirements and physiological demands of the early bovine embryo in vitro. The use of well-defined recombinant proteins might assist in closing this gap.

Animals

mRNA expression of leukaemia inhibitory factor (LIF) and its receptor subunits glycoprotein 130 and LIF-receptor-beta in bovine embryos derived in vitro or in vivo.

Leukaemia inhibitory factor (LIF) plays an essential role during cell differentiation and implantation in the mouse exerting its effects via the two dimerizing receptor subunits glycoprotein 130 (gp130) and LIF-receptor beta (LR-beta). This study investigated the mRNA expression of bovine LIF (bLIF), gp130 and LR-beta in pooled or individual bovine oocytes and embryos generated in vitro or in vivo after superovulation. Transcripts of gp130 and LR-beta were detectable in as little material as 1/3 oocyte equivalent and bLIF transcripts in two embryo equivalents employing a simple, rapid and robust one-step reverse transcription-polymerase chain reaction (RT-PCR) protocol using random hexamer priming during reverse transcription and 60 amplification cycles in the PCR. All mRNA fragments were also found in cumulus cells and various bovine tissues. While gp130 and LR-beta mRNA were present in pooled material throughout embryo development in vitro from the immature oocyte to the hatched blastocyst, bLIF-transcripts were absent in immature oocytes, inconsistently expressed from the matured oocyte up to the 16-cell stage as well as in blastocysts dependent on embryo batch. It was not found in morulae, but again present in hatched blastocysts. In contrast, in in-vivo derived embryos no bLIF was found, LR-beta was not detected at the morula to blastocyst transition while gp130 transcripts were observed from the morula to the hatched blastocyst. In individual embryos the mRNA expression pattern was similar for both in-vitro and in-vivo derived embryos as found in pooled material. These results indicate perturbation of the mRNA expression pattern of the specific LIF-LIF-receptor system in embryos generated in vitro that could lead to abnormal differentiation of the cell compartments forming the blastocyst. Cumulus cells, frequently used as supportive factor in co-culture in bovine in-vitro embryo production, are a rich source of the LIF-LIF-receptor system acting in a paracrine and/or autocrine manner. The biological function of the LIF-LIF-receptor system during bovine preimplantation development warrants further investigation.

Animals

Veterinary parasitology and human health.

Veterinary parasitology is a subdiscipline of veterinary medicine and is concerned (a) with diseases in animals caused by protozoan and metazoan parasites, (b) with parasitic zoonoses and (c) with parasites acting as disease vectors. Veterinary parasitology is related to human health and well-being in a number of ways. It plays a role in treatment, prevention and control of parasitoses in animals which serve as food sources for humans, which are used in agriculture as farm animals or which are companion animals of humans. Of direct significance to human health are activities of veterinary parasitology in prevention and control of food-, water-, vector-borne and other zoonoses, such as toxoplasmosis, cryptosporidiosis, leishmaniosis, taeniosis/cysticercosis, echinococcosis and others. In this context the evolution of veterinary parasitology, progress in the control of parasitic animal diseases, the concerns of mass-treatment of livestock against parasitoses, environment related problems and other factors are discussed. Finally, examples of current and predictable future research trends in veterinary parasitology are summarized. It is concluded that an innovative veterinary parasitology in cooperation with other disciplines will be in a position to contribute further to the improvement of human health and well-being.

Animal Husbandry

Alternatives to animal experimentation in parasitology.

In parasitology, several measures can contribute to the aims of 3R (Reduction, Refinement and Replacement of animal experimentation). These include legal regulations, international guidelines for evaluating antiparasitic drugs, the refinement of animal models for parasitic infections, cryopreservation and cultivation of parasites in vitro or in chicken eggs, the maintenance of arthropods by artificial feeding, and the use of immunological and molecular in vitro techniques (e.g. the production of recombinant antigens for vaccines). Considerable progress has been achieved in the development of alternative techniques but both their standardisation and validation are not far advanced. A wider acceptance and use of alternative methods will only be achieved if research can offer economic alternatives that are as effective and reliable as animal experiments. Great efforts are needed for further progress.

Animal Testing Alternatives

Intraspecific variation of Echinococcus granulosus and related species with emphasis on their infectivity to humans.

Four species are presently recognised within the genus Echinococcus, namely Echinococcus granulosus, E. multilocularis, E. oligarthrus and E. vogeli, which are infective to humans. Evidence for strain diversity within the species E. granulosus, previously mainly based on morphological, biological and biochemical features, has been principally confirmed by recent genetic studies. Several molecular techniques are now available which allow the identification of E. granulosus strains. Epidemiological evidence and molecular studies indicate that the so-called sheep, cattle and cervid strains of E. granulosus are infective to humans, while the horse, camel and pig strains may be less or not infective, but this question warrants further studies. A recent study indicates that E. granulosus infecting patients in Poland shares close molecular affinity with a genotype of pig origin (G7) but exhibits some clear differences. Therefore, it may represent a previously undescribed genotype of E. granulosus, designated as G9. Phylogenetic analysis of molecular data has demonstrated the need to reappraise the taxonomic status of currently recognised strains. Clear evidence for strain variation in the other species of Echinococcus does not exist at present.

Animals

Comparative reproduction of Cryptosporidium baileyi in embryonated eggs and in chickens.

At 2 days of age, each of 20 chickens was perorally or intracloacally infected with 3 x 10(5) oocysts of Cryptosporidium baileyi and maintained for 13 days post infection. In parallel, 20 embryonated chicken eggs were inoculated with 3 x 10(5) oocysts at day 10 of embryonation and were incubated for a further 7 days. The average reproduction rates in the two groups of chickens were x560 after peroral infection and x533 after intracloacal infection as compared with x256 in the eggs. Although the rate of reproduction of parasites seen in the eggs was only about 50% of that observed in chickens, large numbers of oocysts could be harvested (on average, 77 million per egg versus 161 and 168 million from chickens). Nearly the same number of oocysts could be obtained from two eggs as compared with one chicken. The use of embryonated eggs accommodates the sense of animal-protection regulations, is less expensive, and allows the isolation of oocysts under sterile conditions.

Animals

Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus.

Fetal tracheal occlusion accelerates lung growth and corrects the often fatal pulmonary hypoplasia seen in fetuses with congenital diaphragmatic hernia. Fetoscopy presents a unique opportunity to glimpse into the world of the fetus, but its use, until recently, has been limited to diagnostic and simple procedures. Using fetoscopic techniques ("Fetendo"), we now report successful tracheal occlusion in a 30-week-old fetus for the treatment of congenital diaphragmatic hernia.

Adult

Epidemiological investigation of trichinellosis in Switzerland.

Domestic pigs in Switzerland have been considered Trichinella-free for decades, despite the occurrence of Trichinella in the wildlife cycle. In order to reevaluate the present epidemiological situation, tissue samples from 11226 domestic pigs, 356 wild boars and 452 foxes were examined using the standard artificial digestion method. A simultaneous serological study, extended to include 25239 sera from sows provided by a Swiss pig serum bank, was also undertaken. The results of both studies support the conclusion that Trichinella spp. do not occur within the domestic pig population in Switzerland. Among the fox population, Trichinella was detected in four (0.9%) of the animals tested using the digestion method, and Trichinella britovi was identified as the infecting species by RAPD fingerprint analyses.

Animals

Ratio of inner cell mass and trophoblastic cells in blastocysts derived from porcine 4- and 8-cell embryos and isolated blastomeres cultured in vitro in the presence or absence of protein and human leukemia inhibitory factor.

In this study we investigated effects of developmental stage at onset of individual in vitro culture on the progress of development in intact embryos and individual blastomeres derived from 4-cell and 8-cell porcine embryos (referred to as 1/4 and 1/8, respectively), the necessity of serum or BSA supplementation in culture media for embryos and blastomeres (in contrast to development in a defined medium), and the role of two concentrations of human leukemia inhibitory factor (hLIF) on development of blastomeres and embryos. More (p < 0.05) 1/4 blastomeres developed to the blastocyst stage than did 1/8 blastomeres. In the serum-supplemented medium, the percentage of inner cell mass (ICM)/total cells in 8-cell- and 1/8-derived blastocysts was higher (p < 0.05) than that in 4-cell- and 1/4-derived embryos. Development to blastocysts was similar in BSA-supplemented and defined medium as compared to that in serum-enriched medium in intact 4-cell and 8-cell embryos, and 1/4 blastomeres. More (p < 0.05) 1/8 blastomeres developed to the blastocyst stage in serum-supplemented medium than in defined medium. The high hLIF concentration (1000 IU/ml) decreased (p < 0.05) blastocyst development in 1/4 blastomeres in defined medium, but fewer blastocysts (p > 0.05) lacked an ICM (blastocyst-like vesicles) than in defined medium without hLIF. It is concluded that 1) porcine intact embryos and isolated blastomeres can be cultured individually in defined medium up to the blastocyst stage from the 4-cell stage onwards; 2) more 1/4 isolated blastomeres develop to blastocysts with more total cells but with a lower ratio of ICM to total cells than blastocysts derived from 1/8 blastomeres; 3) the effects of hLIF are dependent on proteins present in the culture medium and on the embryonic stage; and 4) in defined medium, high concentrations of hLIF are inhibitory to blastocyst formation, but fewer blastocyst-like vesicles are formed. The defined culture system employed in this study allows examination of the effects of growth factors or cytokines in porcine early embryonic development.

Animals