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Biomedical subjects

J Seifert

Publications and source records attributed to J Seifert.

At least 37 records · Page 2Linked to original sources

[Early death of the severly injured patient--A retrospective analysis].

With 44.9 % trauma is the main cause of death in men under 40 years. From September 3(rd) 1997 to June 30(th) 1998 174 patients with severe injuries or polytrauma were treated in our hospital. The mean ISS was 29 (18-75). 15 (8.75 %) patients died within the first 24 hours. The mean age was 34.5 (2-85) years. The mean ISS of these patients was 48 (25-75). In a retrospective study we analyzed the pattern of injury as well as the preclinical and clinical management. The fact that orthopedic surgery still has got a poor position within the patient's satisfaction-scale and that 15 of 174 analyzed patients had to die within the first 24 hours points out the importance of internal and external quality improvement measurements.

Adolescent↗

Risk of endotoxemia during the initial phase of gut decontamination with antimicrobial agents.

Decontamination of the digestive tract with antimicrobial agents has been used for prevention and therapy of bacterial translocation. With regard to the well-described endotoxin-releasing properties of these agents, the question arises as to whether their enteral administration might result in an increased amount of intestinal endotoxins entering the circulation. Immunocompromised Wistar rats were intraduodenally challenged with live E. coli. Control animals received saline solution, decontaminated rats were treated with either tobramycin plus polymyxin B or ciprofloxacin alone through the duodenal tube. Plasma endotoxin activity and blood bacteria count were measured hourly over an observation period of 5 h. The intestinal bacterial count was determined at the end of the experiment. Gut decontamination in both groups receiving antimicrobial agents resulted in elevated plasma endotoxin levels compared with nondecontaminated controls. Maximum endotoxin levels were found to be 5-6 times higher in the ciprofloxacin group than in the control group and 2 times higher than in the tobramycin/polymyxin group. No positive blood cultures were detected. Intestinal bacterial count was similar in both treatment groups. Enterally applied antimicrobial agents bear an elevated risk of endotoxemia during the initial phase of gut decontamination. The amount of endotoxin translocating from the digestive tract to the circulation varies with the agents used. Polymyxin only partially reduced the observed endotoxin leakage from the gut.

Animals↗

[Emergency diagnosis and emergency care in trauma resuscitation].

Adequate primary and preclinical evaluation of thoracic trauma is the basic for effective therapy. The first intention must be to understand the mechanism of trauma and injury. Severe thoracic trauma is predominantly the result of high energy trauma and mostly combined to multiple injuries (polytrauma). The intention of emergency care medicine is to reduce the number of lethal complications due to trauma. Early intubation and ventilation in preclinical management is accepted as a gold standard. Nevertheless, there is a high percentage of nonintubated and undertreated polytraumatised patients that reach the clinic. To investigate the reason for and problems of undertreatment we have to initiate basic research in accident and polytrauma research.

Adult↗

Synthesis of an alpha-(2,3)-Sialylated, Complex-Type Undecasaccharide.

Only two building blocks were necessary to provide efficient access to the complex undecasaccharide 1 by means of two stereo- and regioselective glycosylation reactions. Stereocontrolled p-methoxybenzyl-assisted beta-mannosylation afforded the critical beta-mannoside linkage in 1, which is a constituent of the human glycoproteins follitropin and gonadotropin.

Journal Article↗

[Detoxification of poly-substance abusers with buprenorphine. Effects on affect, anxiety, and withdrawal symptoms].

We used an open-labeled, 21-day inpatient detoxification treatment to compare the short-term effects of a 10-day buprenorphine plus 19-day carbamazepine regimen (n = 15) to a 14-day oxazepam plus 19-day carbamazepine regimen (n = 12) during rapid detoxification from opioids and other abused drugs. Somatic and psychopathological changes were assessed using the following rating scales: ASI, HAMD, SCL-90-R, and SOWS. Eighteen of 27 patients (67%) completed the study. Four dropouts (27%) were treated with buprenorphine/carbamazepine (BPN/CBZ) and the other five dropouts (42%) were treated with oxazepam/carbamazepine (OXA/CBZ). Repeated measures analysis of variance showed that SOWS scores were significantly less pronounced with BPN-CBZ than with OXA/CBZ. On the first day of admission, no significant difference in HAMD scores was detected (BPN/CBZ 11.6, BPN/CBZ 1.0). On day 14, HAMD was significantly less pronounced in BPN/CBZ (3.0) than in OXA/CBZ (6.1). BPN/CBZ showed a significant improvement in the ASI score on days 7 and 14 compared with OXA/CBZ. Three of nine items of the SCL-90-R showed a trend toward less pronounced outcome in BPN-CBZ. No severe side effects occurred during treatment in either group. The buprenorphine/carbamazepine regimen provided significantly more effective relief from affect disturbances and withdrawal syndromes than the oxazepam/carbamazepine regimen. The pharmacological basis of these effects of buprenorphine (kappa-antagonism activity,mu-agonism activity) are discussed.

Adult↗

Syntheses of alpha-dystroglycan derived glycosyl amino acids carrying a novel mannosyl serine/threonine linkage.

Alpha-dystroglycan (alpha-DG) is a membrane-associated, extracellular glycoprotein. It is anchored to the cell-membrane by binding to the transmembrane glycoprotein beta-dystroglycan (beta-DG) to form an alpha/beta-DG-complex. It was discovered that the bovine peripheral nerve alpha-DG possesses the Ser/Thr linked tetrasaccharide as the major constituent of the O-linked carbohydrates, which was proposed to contribute laminin binding activity of this glycoprotein. This structure has a striking feature in terms of the mode of linkage between oligosaccharide and the core protein. It has a mannose residue linked to the core protein through Ser/Thr residue. A similar structure was proposed to exist in brain derived HNK-1 immunoreactive O-glycans. Being interested in the structural novelty and potential biological significance of this type of glycan chains, the chemical synthesis of Ser/Thr linked mannose containing tetrasaccharide was investigated. Tetrasaccharide donor was constructed from monosaccharide blocks and coupled with Ser/Thr derivatives. Subsequent deprotection afforded target tetraosyl serine. Furthermore, synthetic routes to lower homologues, namely Gal-beta-(1,4)-GlcNAc-beta-(1,2)-Man-alpha-Ser and GlcNAc-beta-(1,2)-Man-alpha-Ser were also provided.

Animals↗

[The importance of the endogenous cannabinoid system in various neuropsychiatric disorders].

The endogenous cannabinoid system was first described in 1988. There are two specific receptors, the CB2-receptor, located in the lymphatic system (spleen, lymphocytes), and the CB1-receptor occurring predominantly in the central nervous system. The CB1-receptor shows a distinct distribution in the CNS with a very high density in the cerebellum, the basal ganglia and in the hippocampus. In 1992 endogenous ligands of the cannabinoid system were discovered for the first time (e.g. anandamide and 2-arachidonylglycerol). The physiological role of these arachidonic acid derivates is still unclear. Implications of these recent discoveries for the Gilles de la Tourette syndrome, ischaemic brain lesions, schizophrenic psychoses and opiate drug dependence are described. A dysregulation in the endogenous cannabinoid/anandamide system could possibly play an import role in the etiology of Gilles de la Tourette syndrome and schizophrenic psychoses; administration of cannabinoids affects the symptoms of the Gilles de la Tourette syndrome positively, whereas cannabinoids probably have rather negative effects in schizophrenic psychoses. In ischaemic brain lesions cannabinoids seem to have a neuroprotective effect; they appear to minimize the extent of a lesion by reduction of glutamate release. Additionally the meaning of the endogenous cannabinoid system for the development of opioid drug dependency is discussed and interactions between the endogenous opioid system and the endogenous cannabainoid system are pointed out. This is of interest since it could be shown in animal experiments that the absence of CB1 receptors reduces the positive reinforcement of opiate administration.

Animals↗

Protective capacity of a IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia.

Animal experiments were carried out to investigate whether a protective effect can be achieved in endotoxemia by intravenous (i.v.) application of a polyclonal immunoglobulin preparation (IVIG-IgG/A/M) enriched with 12% IgM and 12% IgA. Following administration of IVIG-IgG/A/M (500 mg/kg), endotoxemia was induced by intraperitoneal inoculation of a sublethal dose (5x10(8) CFU/kg) of Escherichia coli (E. coli) and subsequent i.v. administration of an antimicrobial agent (Imipenem). Plasma endotoxin activity, IL-6 activity, mean arterial pressure, and skeletal muscle oxygen pressure (tpO2) were measured at regular intervals over a total observation period of 7 h. Prophylactic administration of IVIG-IgG/A/M was found to significantly attenuate (P<0.01) the antibiotic-induced increase in endotoxin activity as compared to the albumin control group. Limited endotoxemia in the IgG/A/M group was associated with reduced levels of circulating IL-6 (P<0.01). Both lipopolysaccharide-induced hypotension and depression of tissue oxygenation were attenuated (P<0.01) by pre-treatment with IVIG-IgG/A/M. The experimental results suggest that in endotoxemia the polyclonal immunoglobulin preparation has a prophylactic protective effect on the acute phase responses and reduces the cardiodepressant effects of E. coli septicaemia.

Animals↗

Oral administration of (14)C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL).

Several investigations showed a positive influence of orally administered gelatin on degenerative diseases of the musculo-skeletal system. Both the therapeutic mechanism and the absorption dynamics, however, remain unclear. Therefore, this study investigated the time course of gelatin hydrolysate absorption and its subsequent distribution in various tissues in mice (C57/BL). Absorption of (14)C labeled gelatin hydrolysate was compared to control mice administered (14)C labeled proline following intragastric application. Plasma and tissue radioactivity was measured over 192 h. Additional "gut sac" experiments were conducted to quantify the MW distribution of the absorbed gelatin using SDS-electrophoresis and HPLC. Ninety-five percent of enterally applied gelatin hydrolysate was absorbed within the first 12 h. The distribution of the labeled gelatin in the various tissues was similar to that of labeled proline with the exception of cartilage, where a pronounced and long-lasting accumulation of gelatin hydrolysate was observed. In cartilage, measured radioactivity was more than twice as high following gelatin administration compared to the control group. The absorption of gelatin hydrolysate in its high molecular form, with peptides of 2.5-15kD, was detected following intestinal passage. These results demonstrate intestinal absorption and cartilage tissue accumulation of gelatin hydrolysate and suggest a potential mechanism for previously observed clinical benefits of orally administered gelatin.

Administration, Oral↗

[Significance of the absorption of macromolecules for the immune response of an organism].

Numerous antigens are offered to the living organism by the daily food. With these investigations the influence of orally administered human gammaglobulin (HGG) on the immunity of sensitized animals after systemic immunization should be clarified. Experiments were performed in rabbits. Changes of the circulation were measured by bloodpressure registration and measurements of the organ flow. Simultaneous investigations of the antibody content, complement C3 and histamin were performed in the peripheral blood. In orally fed animals as well as in non fed controls an i.v. antigen challenge was performed. The level of circulating antibodies could be significantly decreased (60%) by the oral administration of HGG. In control animals the parenteral antigen challenge resulted in a mortality rate of 50%. In these animals the bloodpressure decreased significantly and long lasting, whereas antigen fed animals showed only a slight change in bloodpressure with normalization after a short period. During oral absorption of antigen complement factor C3 remained unchanged. In the first hour after the oral antigen administration a significant increase of histamin in the peripheral blood could be observed. Investigation with regard to the fate of the antibodies which were decreased by antigen feeding showed a storage in the layers of the gut which was depending on the dosage. It could be demonstrated that it is possible to influence the systemic immune response by the enteral application of macromolecules and this is also relevant for reactions of the circulation.

Animals↗

[Studying minimally invasive osteosynthesis methods for distal radius fractures. Intra-focal vs. conventional wire osteosynthesis].

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.

Adult↗

New arguments to explain the high infection rate in posttraumatic spleenless patients.

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.

Adult↗

The influence of Roux-Y versus Longmire-Gütgemann reconstruction on the composition of pancreatic juice.

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.

Alkalies↗

Changes of volume substitution for the treatment of hemorrhage within 10 years and their costs.

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.

Albumins↗

[DNA content of the tumor cell. A new prognostic parameter in hepatocellular carcinoma?].

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.

Adult↗

Methyl and phenyl esters and thioesters of carboxylic acids as surrogate substrates for microassay of proteinase K esterase activity.

The development of a microassay for proteinase K esterase activity with carboxylic acid esters is reported using novel substrates of the general formula R-C(O)-XR'. Highest rates of hydrolysis have been obtained with the O-phenyl esters CH(3)(CH(2))(n = 1 - 2)-S-(CH(2))(n = 1 - 2) C(O)-O-phenyl and their thioester analogs in studies where R, X and R' have been varied. The phenol release has been measured with 4-aminoantipyrine and potassium ferricyanide to determine the rates of O-phenyl ester hydrolyses. Thioester hydrolyses have been monitored continuously with 5,5'-dithio-bis (2-nitrobenzoic acid).

Journal Article↗

Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry.

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.

Animals↗