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Biomedical subjects

J Eckert

Publications and source records attributed to J Eckert.

At least 163 records · Page 9Linked to original sources

Killing of Giardia lamblia by human milk is mediated by unsaturated fatty acids.

Giardia lamblia trophozoites were killed in vitro by 1% fresh human milk in the presence of bile. A similar effect was achieved in the absence of bile with milk which had been stored for at least 24 h at 6 degrees C. This killing activity was found to be caused by unsaturated fatty acids. Depending on their chain length and the number of double bonds, the concentrations of unsaturated fatty acids required for a 50% killing effect varied between 15 and 36 microM. The saturated palmitic and stearic acids, as well as various substances related to fatty acids, showed only a slight killing effect. Bile enhanced and serum suppressed the action of fatty acids on the protozoan parasite. The possible site of interference of unsaturated fatty acids within G. lamblia and the reasons for the obvious inefficacy of dietary fatty acids in giardiasis are discussed.

Adult↗

Treatment of cystic echinococcosis (Echinococcus granulosus) with mebendazole: assessment of bound and free drug levels in cyst fluid and of parasite vitality in operative specimens.

Chemotherapy of the larval stage of Echinococcus granulosus in man with high oral doses of mebendazole has only been partly successful. In order to improve effective pharmacotherapy of this disease with mebendazole, the optimal time for blood sampling has been assessed and the mebendazole concentrations acting on the parasite have been compared with their viability. The optimal time for blood sampling was analysed in 14 patients during longterm treatment with mebendazole. The plasma level 4 h after the morning dose exhibited the best correlation with the average 24-h concentration, suggesting that the plasma level should be monitored 4 h after the morning dose. In 22 patients undergoing surgery for hydatid disease, the mebendazole concentration in cyst fluid was significantly correlated with its plasma level 4 h after the morning dose. In 13 of them the free drug concentration was determined by equilibrium dialysis and it was almost identical with the free mebendazole concentration in plasma. Results of viability tests in 12 cases revealed viable cysts in 6 cases and possibly viable cysts in 6 other cases. Even patients treated for more than 12 months still had viable cysts.

Adult↗

Cryopreservation of Echinococcus multilocularis metacestodes and subsequent proliferation in rodents (Meriones).

Four isolates of larval Echinococcus multilocularis originating from Switzerland (CH/1, CH/6 and CH/22) and Alaska (A/1) were used to prepare crude homogenate or small tissue fragments (STF) in Eagle's Minimal Essential Medium with Earle's salts (EMEM/A), or 0.2 g tissue blocks (TB) which were suspended in the same medium. After addition of dimethylsulfoxide or glycerol in final concentrations of 5% and 10% (v/v), respectively, aliquots of 1.0 ml, containing either 0.1 ml crude homogenate or STF, or one block of 0.2 g, were kept in cryotubes for 30 min at +2-4 degrees C (precooling phase), cooled subsequently to lower temperatures following a two-step or three-step schedule and finally plunged into liquid nitrogen (-196 degrees C). After storage for one week the samples were rapidly thawed at +37 degrees C for approximately 3 min, washed in fresh EMEM/A (37 degrees C) and transferred into the peritoneal cavity of Meriones for viability testing. As judged by histological examinations and metacestode weights of each 24 Meriones infected with cryopreserved homogenate, STF or TB, respectively, 46%, 87% or 100% contained viable, proliferating parasites. The best proliferation rate occurred when 10% glycerol was used as cryoprotectant and after precooling a three-step freezing schedule was employed (30 min at -28 degrees C, 30 min at -80 degrees C, transfer to liquid nitrogen). Cooling rates were determined as 0.7, 1.0 and 1.7 degrees C min-1 for the precooling phase, step 1 and step 2, respectively, and estimated as 65 degrees C min-1 for step 3. These results demonstrate that metacestodes of E. multilocularis can be successfully maintained by cryopreservation without losing their proliferative capacity in the intermediate host.

Animals↗

Effect of plasma mebendazole concentrations in the treatment of human echinococcosis.

High oral doses of mebendazole were given for a mean period of 23 months to 22 patients with inoperable alveolar or cystic echinococcosis (Echinococcus multilocularis n = 18, E. granulosus n = 4). Clinical, morphological, biochemical and serological findings and plasma mebendazole levels were monitored. Clinical and biochemical improvement or stabilization was observed in 17 patients but the parasitic lesions did not decrease in size in most instances. One patient died shortly after onset of therapy with hemorrhage of esophageal varices. Three patients with alveolar and one with cystic echinococcosis had evidence of progressive disease such as increase of cholestasis, destruction of lumbar vertebrae and growth of an intraperitoneal cyst. The plasma mebendazole levels (4 hr after the morning dose) of the latter 4 patients were 0.09 +/- SD 0.02 mumol/l, while in those with clinical stabilization or improvement it was 0.30 +/- SD 0.14 mumol/l (P less than 0.001). These preliminary data indicate 1) a good clinical response to chemotherapy in most patients despite unchanged size of the parasitic lesions, and 2) a direct correlation of clinical response with plasma mebendazole levels.

Adult↗

Determination of parasite-specific immunoglobulins using the ELISA in patients with echinococcosis treated with mebendazole.

Parasite-specific immunoglobulin classes were determined by the ELISA in sera of 19 patients with cystic or alveolar echinococcosis before and after 2 years (+/- 4 months) of continuous treatment with mebendazole at daily doses of 35-50 mg/kg body weight. In the majority of cases IgG decreased and IgA and IgE decreased or disappeared. In contrast, four patients with progressive disease showed reverse tendencies with increasing IgG, IgA and IgE concentrations during the same period.

Animals↗

[Chemotherapy of human echinococcosis].

In human echinococcosis, today as in the past, surgical removal of the parasite remains the treatment of choice. Beside certain conditions, adjuvant chemotherapy with Vermox is indicated for echinococcus multilocularis as well as echinococcus granulosus. A substantial decrease of the echinococcal parasite mass under Mebendazole is not yet known. Nevertheless jaundiced patients with diffuse liver infestation with echinococcus multilocularis became jaundice-free and able to work. Mebendazole toleration is very good. A closely interrelated medical control of patients under Mebendazole therapy ought to be interdisciplinarily carried through between internists and surgeons.

Administration, Oral↗

Proliferation and metastases formation of larval Echinococcus multilocularis. I. Animal model, macroscopical and histological findings.

Using surgical techniques, 70 Meriones unguiculatus were infected by implantation of 0.15-0.20 g of larval Echinococcus multilocularis tissue into the subcutis of the neck region. In 64 of 65 animals necropsied, the transplants had increased in size and weight and reached an average weight of 4.1 g at the end of the experiment 12 weeks post infection (p.i.). Metastatic Echinococcus lesions developed in the regional lymph nodes and in the lungs; in 18 animals the parasite proliferated into the thoracic cavity. Of 41 animals examined 10 and 12 weeks p.i., 88% had multiple or single metastatic lung lesions, the first being observed 6 weeks p.i. Typical cysts and protrusions ("buds") of the germinal layer were detected in samples of parasite tissue before and after transplantation to experimental animals, as well as in lymph nodes and lungs in which metastases had developed. Similar structures were found in liver sections of two patients with alveolar echinococcosis. It is concluded that the spread of the parasite from the subcutis of the neck region to the draining lymph nodes and the lungs had taken place via the lymph and blood system. The possible role of the "buds" in metastases formation is discussed.

Animals↗

Proliferation and metastases formation of larval Echinococcus multilocularis. II. Ultrastructural investigations.

The larval stage (metacestode) of Echinococcus multilocularis was studied by means of electron microscopy (SEM, TEM) before and after subcutaneous transplantation to jirds (Meriones unguiculatus) and in their lymph nodes and lungs with parasite metastases. It was found that the metacestode consists of a network of solid, cellular protrusions (buds) of the germinal layer which transform to tube-like and cystic structures devoid or with a laminated layer. Proliferation of the metacestode apparently occurs by protruding filamentous solid cell columns (buds) from the germinal layer. Their tips have diameters of only one cell: they are covered with a smooth syncytial tegument without microtriches and are filled with undifferentiated cells which contain a nucleus with a large nucleolus. The tegument is constantly enlarged by fusion with the underlying undifferentiated cells that divide repeatedly. At some distance from the tip a cavity develops inside the protrusion, thus finally giving rise to a tube-like structure which may transform to a cystic expansion. Simultaneously, the surface of the protrusion changes by the formation of microtriches and the occurrence of an amorphous laminated layer. The latter is concentrically covered by connective tissue cells and large amounts of collagen. Within cyst-brood capsules, finally protoscoleces are formed from accumulations of undifferentiated cells beneath the tegument. The study has unequivocally proven the cestode nature of the cellular protrusions, and it is assumed that detachment of cells from these structures and their subsequent distribution via the circulation may play a role in the formation of metastases. The origin of the laminated layer is discussed.

Animals↗

Observations on Echinococcus multilocularis in the definitive host.

Six dogs were found to be susceptible to experimental infections with a European isolate of Echinococcus multilocularis from southern Germany. Two cats were only poorly susceptible. Adult worms were not evenly distributed throughout the small intestine and the majority of parasites were found in the posterior region. The mode of attachment of E. multilocularis in the dog was similar to that for E. granulosus with the adult worm extending its rostellum deep within a crypt of Lieberkühn. In cats only few worms were found to have penetrated deeply between the villi. E. multilocularis was found to possess a modified group of rostellar tegumental cells, morphologically and functionally identical to those described in E. granulosus and previously referred to as the "rostellar gland". By studying development in vivo and in vitro, the time required for the production of shelled eggs was demonstrated to be only 28 days. Concurrent experimental infections in dogs with E. multilocularis and E. granulosus revealed that both species will develop together in the same host. Their development was not retarded in any way by the presence of the other and both species were able to coexist in the same area of the intestine.

Animals↗

Serological differentiation between Echinococcus granulosus and E. multilocularis infections in man.

An enzyme-linked immunosorbent assay (ELISA) was adapted for the serological differential diagnosis of cystic or alveolar echinococcosis in man caused by Echinococcus granulosus or E. multilocularis respectively. By affinity chromatography using rabbit anti hydatid fluid IgG coupled covalently to CNBr-Sepharose 4B a protein fraction (Em 1) containing shared antigens of both parasites could be isolated from an extract of E. multilocularis metacestode tissue. From the same source another antigen fraction (Em 2) with a high degree of specificity for E. multilocularis was prepared by immunosorption. Antigen Em 1 was equally sensitive for the detection of antibodies against E. granulosus and E. multilocularis, whereas antigen fraction Em 2 appeared to be more specific for E. multilocularis. A correct serological differential diagnosis was achieved in 95% of 57 confirmed cases of human cystic or alveolar echinococcosis by the simultaneous use of both antigen fractions in the ELISA and by comparison of their reactivities.

Animals↗