Fibrin sealant, aprotinin, and immune response in children undergoing operations for congenital heart disease.
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Publications and source records attributed to J Seifert.
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From 1992 to 1995 126 patients were treated with percutaneous wire pinning. Sixty-one patients were treated by Kapandji's technique and 65 patients were treated conventionally. Forty-nine patients were examined by 3 different scores (Cooney, Castaing, Stewart). The analysis of the scores showed no differences between the Kapandji technique and the conventional method. Functional and radiological results showed no correlation. Furthermore we found out that the results depend on the score. We conclude that the Kapandji technique shows no benefit in comparison to the conventional method. Functional and radiological results are not divisible: a conclusion from X-ray to function and vice versa is not allowed. A comparison of results is senseless if someone does not use the same score.
To get more information about the high infection rate in splenectomized adult patients 211 spleenless patients were investigated with regard to clinical and laboratory data and compared to healthy blood donors. The results show that the infection rate is markedly increased to 30%. Splenectomized patients have decreased IgG levels which is due to diminished IgG1 and IgG4. Whereas IgA, complement factors C3, C4, and transferrin are not changed in patients without spleen, fibronectin and IgM are significantly reduced and the phagocytosis as well as the migration of neutrophilic granulocytes is impaired to 50%. With these changes in laboratory data it is possible to identify patients which bear an increased risk with regard to infection.
Both methods of reconstruction after gastrectomy lead more or less to an insufficiency of pancreas. Therefore investigations on rats should further clarify which defects are obvious after both operation methods. Wistar rats were divided into 3 groups. In 2 groups a gastrectomy was performed while one was reconstructed according to the method of Roux-Y, the other was treated according to the method of Longmire-Gütgemann. The first group was a sham operated control group. 3 months after this operation pancreatic juice was collected over the time of 6 hours. Volume and protein content were determined as well as a differentiation of the proteins by means of the 2D electrophoresis which separates the molecules according to isoelectric focus and the molecular weight. The results show a significant increase of the volume of pancreatic juice after both operations. Whereas the protein content is also altered the number of proteins is significantly decreased. Especially proteins with an alkaline isoelectric focus are significantly diminished. The molecular weight of the proteins is also changed. Low molecular protein fragments which were not observed in the sham operated group are increased especially in the Roux-Y group. This means that the production of enzymes is changed after both operations. The pH optimum as well as the viability of the protein enzymes is shifted. Since the changes are more pronounced after Roux-Y operation signs of pancreatic insufficiency should be expected more frequently after this operation.
Whereas 10 years ago blood loss was substituted by whole blood application together with colloidal or crystalloid substitutes, this behavior changed to a distinct therapy according to the changed laboratory parameters with the application of red cell concentrates together with fresh frozen plasma (FFP). By means of two representative operations (resection of sigma and hemicolectomy) the behavior of volume application and the substitution of blood and blood components were controlled for the years 1980 and compared with the behavior of 1990. In addition to that the costs for both behaviors were calculated and compared. The volume substitution of altogether 176 patients was investigated. 87 patients were operated in the year 1980 and 89 patients in the year 1990. 60% sigma resection were observed on both decades. The analysis revealed that the main substitute (60%) was whole blood in the year 1980 whereas in the year 1990 only 3% of the patients were treated with whole blood. A reverse development was observed with the application of red cell concentrates which was only 2% in the year 1980 but 54% in the year 1990. Unexpectedly the consumption of FFP remained nearly constant in both decades whereas the administration of 5% albumin increased from 40% to 80%. Also the behavior with regard to colloidal substitutes changed markedly within the 2 decades. Dextran and gelatin preparations were exclusively applied in the year 1980 and starch preparations in mainly the year 1990. This changed behavior was responsible for an increase of the costs of 100 $US for every patient. Although the changed behavior can be explained with advantages for the patient but this must be paid by an increase of the costs.
Hepatocellular carcinoma is a heterogeneous disease with considerable differences in malignant behaviour. Some relevant factors for prognosis are known. In this study we analysed DNA ploidy as a potential prognostic parameter. With DNA image cytometry we were able to differentiate between diploid, hypotriploid, triploid, hypertriploid, tetraploid and aneuploid tumours. The best prognosis was for patients with diploid, hypotriploid and tetraploid tumours with a median survival time of 41 months in contrast to 3 months for patients with triploid, hypertriploid or aneuploid tumours. There was a strong correlation between histomorphological parameters and the DNA content. The DNA content of tumour cells may be considerable clinical relevance in hepatocellular carcinoma regarding the decision as to whether or not to perform a resection. In patients with prognostically unfavorable parameters adjuvant oncological therapy may improve the prognosis.
SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug combinations.
We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.
From January 1985 till December 1994 109 patients with rectal carcinoma were treated by local excision, in 36 patients a radical operation was performed afterwards. In the assessment of tumor infiltration endosonography was superior to rectal-digital examination. In 34 patients with local excised "low risk" T1-carcinomas and tumor free margins no local recurrence was observed. Two of ten patients with local excised "low risk" T1-carcinoma and no adequate margin of healthy tissue developed a local recurrence. Regarding our results the local excision of "low risk" T1-carcinomas seems justified, if final histological workup reveals an adequate margin of healthy tissue.
This is a report of a rare case of an isolated fracture of the trapezium. Origin, diagnosis, differential diagnosis, treatment and complications are evaluated and described.
The bioavailability of polystyrene particles (1 microns) labelled with FITC (3M Company, Düsseldorf) was tested in rats after enteral administration. Since macromolecules and particles are preferentially transported in the lymph, the number of particles was counted in the lymph of the thoracic duct over a 6 h period. Uptake in young rats (6-8 wk) was compared with that in 5 and 9 mo animals. Young animals absorbed only 87 particles whereas a marked increase in the uptake of particles was observed in 5 mo animals (up to 775) but there was a decrease to 518 particles in older animals (9 mo). This number of particles is the total number of the entire output of the thoracic duct lymph over a 6 h period. In individual animals this number showed a considerable fluctuation over time. The volume of the collected lymph fluid was relatively constant (3.5 +/- 0.5 ml) in all animals. The bioavailability of the particles in the lymph was also influenced by the applied dose of particles. After intraduodenal administration of 3.7 x 10(5) particles only 18 particles could be found in the lymph. Increasing the dose to 3.7 x 10(7) particles raised the number of particles in the lymph to 116. The highest dose of 3.7 x 10(9) was correlated with the greatest absorption, 775 particles being found in the lymph. The uptake of particles from the gut thus depends on different factors including the age of the animal and the number of applied particles.
The aim of this study was to influence the translocation of microorganisms and endotoxin from the gut of septic rats by the intravenous (i.v.) administration of immunoglobulin and interleukin 2. Acute infection was induced in all animals by an intraperitoneal bacterial challenge of 2 x 10(6) microorganisms (Ps. aeruginosa, E. coli, Kleb. pneumoniae). Immediately after the bacterial challenge control animals were given albumin i.v. whereas the experimental groups were given immunoglobulin or interleukin 2. A significant reduction of bacteria in the plasma of rats was observed in immunoglobulin treated animals (10,000 CFU/ml vs 450 CFU/ml). This was accompanied by an increase of plasma endotoxin of nearly 100% within the first 2 h. Interleukin 2 essentially did not change the bacterial count in comparison with albumin-treated control animals but reduced the endotoxin level in plasma up to tenfold. It is concluded that both immunoglobulins and interleukin 2 are involved in severe infections. Whereas immunoglobulins reduce bacterial translocation, interleukin 2 stimulates the elimination of endotoxin.
A new model of metastatic liver tumors in Wistar/Furth rats is introduced. A colorectal adenocarcinoma cell line (LDLX40) induced by 1,2-dimethylhydrazine was injected through one of the branches of the ileal mesenteric vein to develop metastatic liver tumors in rats. On day 30 after the inoculation of tumor cells, micrometastases were detected under microscopy in all animals that received tumor inoculation. Macrometastases in 87.7% of animals were found by either the tumor staining test or ultrasonography. No extrahepatic tumor developed in this tumor model. To observe the effects of different treatment strategies on metastatic liver tumors, 35 animals were randomly divided into four groups. Group I served as control. Group II underwent hepatic artery ligation (HAL). Group III received intraportal administration of recombinant interleukin-2 (rIL-2) and interferon-alpha (IFN-alpha). Group IV had intraportal medication of rIL-2 and IFN-alpha + HAL (the IIH protocol). Results indicated that rapid tumor growth was seen in the control tumors. HAL produced little response to metastatic liver tumors as compared to the control group (P > 0.05). The combined application of rIL-2 and IFN-alpha showed an improved result, with 22% of tumor growth inhibition or regression (P < 0.05 compared to the control group). Twenty-eight percent of tumor growth restraint or regression was found in the group treated with the IIH protocol (P < 0.05 compared to the control group). We conclude that this new experimental model of metastatic liver tumors is reproducible, and that the IIH protocol is effective in the treatment of metastatic liver tumors in rats. These beneficial effects from the IIH protocol may be introduced into patients with metastatic liver tumors.
Two modifications in this study, including the use of subcutaneous transposed spleen (STS) as a port for administration of recombinant interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and the mixture of IL-2 and IFN-alpha with degradable starch microspheres (IIM), for the treatment of rat liver tumor are introduced. Group I is the control. Group II received the IIM schedule through the STS. Group III and group IV received IL-2 and IFN-alpha, diluted with normal saline and injected through the STS or a peripheral vein. The comparative studies indicated that the best result was seen in group II where the elevated concentration of IL-2 in portal blood and massive tumor necrosis with lysis were observed. Inhibitions of tumor growth of 33%, 20% and 13% in group II, III, and IV, respectively, were observed. We conclude that administration of the IIM schedule through the STS is an effective method for the treatment of liver tumor in rats.
This study tested the effect of intratumoral injection with activated tumor-infiltrating lymphocytes (TIL), and simultaneous administration of recombinant interleukin-2 (rIL-2) and interferon alpha (IFN-alpha) (LII protocol), on mouse liver tumor. Group I (n = 10) served as the controls. Group II (n = 17) received rIL-2 + IFN-alpha schedule. Group III (n = 20) received the LII protocol. A total of 5 x 10(6) of TIL were injected into 4 sites of a tumor in a single treatment. rIL-2 (1 x 10(6) IU) on the first day and IFN-alpha (1 x 10(5) IU) on the second day were alternately given with a total of 10 treatment doses that were completed in 20 days. Tumor remission or regression rates of 29% and 40% were obtained in groups II and III, respectively, but no remission was obtained in the controls. A large number of TIL were also observed in the tumors treated with the LII protocol. Making comparisons between the control group and IL-2 + IFN-alpha schedule, and the control group and LII protocol, the ratios of cytolytic activity of TIL in vitro were 0:32 and 0:57, respectively. We conclude that the LII protocol appears to be more effective in the treatment of mouse liver tumor than the IL-2 + IFN-alpha schedule, and that it may be a new promise for the treatment of patients with liver malignancies.
Three isomers of trifluoromethylaniline (TFMA) were investigated for their possible different toxic effects on the hematopoietic system in male Wistar rats. The effects of isomeric 2-, 3- and 4-TFMA were compared with those of aniline, the prototypic drug. Strong leukocytosis manifested by considerable increase in the number of all respective white blood elements was observed in the peripheral blood 1 day after the administration of 4-TFMA. In contrast, erythropoiesis, as ascertained by erythrocyte count and hemoglobin concentration, was inhibited by 4-TFMA. The determination of the ED50 revealed lymphocytes to be the most responsive elements towards 4-TFMA administration. Besides hyperemic and proliferative splenomegaly the histological changes in maturation of immunocompetent cells following the 4-TFMA administration were found also in thymus. In accord with an enhanced incorporation of [3H]thymidine, the specific activity of thymidine kinase (TdK) in spleen was increased after a single dose of 4-TFMA. Activities of the catabolic enzymes adenosine deaminase (ADA) and inosine phosphorylase (IP) decreased in both organs with the exception of IP activity in thymus. The effects evoked by the 3-TFMA isomer were regularly less pronounced, and 2-TFMA was nearly inactive.
It has been reported that coagulation factor VIII (F. VIII) is produced in the spleen and other organs. Transplantation of splenic whole organ and spleen cells may, therefore, be used to treat patients with hemophilia A. The donor spleen from brain-dead donors was used to prepare spleen cell suspension for transplantation. Twenty-two spleen cell transplantations were performed on 20 patients suffering from severe hemophilia A at our institutes. Two of them underwent a second infusion of spleen cells since there was no increase in plasma F. VIII activity after the first transplantation. All but two patients showed a marked clinical improvement. Increased plasma F. VIII activity was observed in 18 of 20 cases. The peak plasma F. VIII activity in these recipients rose to 10%-15% posttransplantation in 14 cases and to over 15% in 4 cases from pretransplant levels of 0%-3%. Generally, the elevation of plasma F. VIII activity could be detected 4-7 days following transplantation of spleen cells and this lasted from 22 to 58 weeks. Four patients whose peak plasma F. VIII activity was greater than 15% experienced an uneventful course after transplantation. The patients with plasma F. VIII activity over 10% showed less frequent bleeding and prolonged intervals between bleed as well as improvement in hemophilic arthrosis. Two patients who had interval hematuria before transplantation did not have any relapse for up to 2 years after infusion of the spleen cells. These results indicate that spleen cell transplantation may be a promising method for the management of patients with hemophilia A.
Membrane-bound neuropathy target esterase (NTE) and associated phenyl valerate carboxylesterases were solubilized from chicken embryo brain by phospholipase A2. Phospholipase A2 from bee or cobra (Naja) venoms were the most effective preparations in solubilizing brain NTE and other phenyl valerate carboxylesterases. Phospholipase C and several proteinases (endoproteinase, pronase E, proteinase K, thermolysin, trypsin) did not solubilize brain membrane-bound carboxylesterases but reduced their activity. NTE solubilization by phospholipase A2 did not affect its apparent Km and Vmax for the substrate phenyl valerate or the susceptibility of phenyl valerate carboxylesterases to inhibition by paraoxon and mipafox. NTE thermal stability diminished after the treatment of brain membrane fragments with phospholipase A2.