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Biomedical subjects

M Siebeck

Publications and source records attributed to M Siebeck.

At least 55 records · Page 3Linked to original sources
PubMed1992

Accurate diagnosis of acute appendicitis: a retrospective and prospective analysis of 686 patients.

OBJECTIVE: To formulate a score system that would make the preoperative diagnosis of acute appendicitis more accurate. DESIGN: Retrospective then prospective study. SETTING: City University Hospital. SUBJECTS: 536 patients who had their appendixes removed between 1981 and 1986 (retrospective study), and 150 consecutive patients admitted with a presumptive diagnosis of appendicitis between 1987 and 1988 (prospective study). MAIN OUTCOME MEASURES: Correlation between the histological diagnosis of appendicitis and variables representing history, clinical examination, and laboratory investigations. RESULTS: The rate of histologically proven negative appendicectomies in the retrospective series was 40% and in the prospective series 33%. The variables that were thought to be predictive were: male sex, white cell count of greater than 11 x 10(9)/l, history of less than 24 hours with no previous complaints, rebound tenderness, shift of pain from the epigastrium, and localised guarding, but all criteria had low specificities and sensitivities when applied prospectively, and combining the scores did not improve them. CONCLUSION: The accurate diagnosis of appendicitis depends largely on the experience of the surgeon and is not improved by the application of a score system that includes the above variables.

Acute Disease↗
PubMed1992

[The value of extended resection in locally advanced bronchial carcinoma].

A retrospective study on 68 patients with non-small-cell lung cancer (NSCLC) treated by extended resections is presented. Compared to simple resections extended resections carried a higher risk for postoperative complications, whereas 30-days-mortality was not influenced by type of resection. Analysis of survival rates after extended resections revealed no influence by T- or N-stage, whereas a residual tumor lowered the survival rates significantly. Overall, a 2-year-survival rate of 35% was observed after extended resections. In conclusion, even in locally advanced cases of NSCLC a resection with curative intent seems to be warranted, provided that a R0-stage can be achieved by surgery.

Carcinoma, Bronchogenic↗
PubMed1991

A purified antithrombin III--heparin complex as a potent inhibitor of thrombin in porcine endotoxin shock.

Inhibition of activated clotting factors is an important therapeutic approach in disseminated intravascular coagulation (DIC). We examined the possible protective effect of a purified complex of human antithrombin III (AT III) and heparin in endotoxin-induced DIC in pigs. Two groups of endotoxemic pigs were studied. AT III-heparin group pigs (n = 8) were pretreated with a bolus injection of 500 units AT III-heparin complex, followed by a continuous infusion of 1000 units of the complex for 6 hours given simultaneously with the infusion of 10 micrograms/kgh of S. abortus equi endotoxin. Controls (n = 9) were given saline in addition to the continuous infusion of endotoxin. AT III activity, prothrombin and soluble fibrin in plasma were determined by chromogenic substrate methods. Fibrinogen was measured turbidimetrically. Human AT III antigen in the treated group was 64 +/- 3% at 2 hours and increased to 84 +/- 4% until the end of the experiment. AT III activity in the AT III-heparin group was elevated throughout the whole observation period (greater than 100%), whereas it was significantly lower in the controls. Prothrombin decreased similarly in both groups by approximately 35% until the end of the experiment. AT III-heparin treatment significantly attenuated the endotoxin-induced consumption of fibrinogen and completely prevented the increase in soluble fibrin in plasma. However, no significant effect of AT III-heparin was observed on endotoxin-induced mortality and dysfunction in pulmonary gas exchange. Therefore we conclude that the purified AT III-heparin complex inhibits thrombin effects and prevents development of DIC, but fails to significantly influence clinical outcome in endotoxin shock of the pig.

Animals↗
PubMed1991

Determination of thrombin-hirudin complex in plasma with an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of the thrombin-hirudin complex (TH) in plasma. The test is based on the sandwich principle and uses appropriate antibodies which selectively bind the corresponding moieties of the complex. The assay was calibrated by adding performed TH to normal human citrated plasma. The detection limit of the assay was 1.2 ng/ml. Mean coefficients of variation of 6.0% (intra-assay) and 6.4% (inter-assay) were found. The presence of TH was demonstrated in normal human plasma that was spiked with hirudin and subsequently activated in vitro by calcium-thromboplastin to generate thrombin. This complex was also found in plasma samples from pigs which had been treated with hirudin during experimentally induced septicaemia.

Animals↗
PubMed1991

Time dependent release of tissue-type plasminogen activator and plasminogen activator inhibitor into the circulation of pigs during shock.

To investigate short-term activation and inhibition of fibrinolysis during shock, we studied plasma levels of tissue-type plasminogen activator (t-PA) and t-PA inhibition capacity (PAI) in anaesthetized pigs. t-PA in euglobulin fractions of plasma was measured by the conversion of plasminogen to plasmin in the presence of fibrin split products. Plasmin thus generated was measured in a chromogenic substrate assay. PAI was measured as plasma inhibition capacity for human melanoma t-PA. Controls (n = 8) had constant t-PA and PAI for 6 h. Lipopolysaccharide from Salmonella abortus equi in four different doses (n = 9 - 11), or live Escherichia coli (n = 3) induced a transient t-PA increase with peak values at 2 h. PAI decreased to 50% at 2 h and increased to 250% at 6 h. Phorbol myristate acetate (n = 7) induced no change of t-PA or PAI. Dextran sulphate (n = 4) produced a t-PA rise at 30 min, followed by a rapid decline. Endotoxin was an appropriate stimulus for activation and inhibition of fibrinolysis whereas phorbol ester failed to elicit this response.

Animals↗
PubMed1991

A triazolodiazepine platelet activating factor receptor antagonist (WEB 2086) reduces pulmonary dysfunction during endotoxin shock in swine.

We wanted to determine the effects of WEB 2086, a platelet activating factor (PAF) antagonist, in lipopolysaccharide (LPS) shock in anesthetized pigs. In a randomized study, LPS from S. abortus equi, 2 micrograms/kg/h was given IV for six hours. Thirteen animals received LPS and WEB 2086, 10 mg/kg/h IV for 6.5 hours, beginning 30 minutes before LPS. Eleven septic controls received saline and LPS, three nonseptic controls received saline and WEB 2086, and three nonseptic controls received saline only. In six animals we investigated the effect of synthetic PAF in doses between 50 and 10,000 ng on arterial (AP) and pulmonary arterial (PAP) pressure before and during infusion of WEB 2086. The LPS-induced rise in PAP was reduced by WEB 2086 (p = 0.01) but not the decrease in AP. The LPS-induced leukopenia, hypoxia, increase in airway pressure, and release of plasminogen activator inhibitor were reduced by WEB 2086. Platelet activating factor produced an increase in PAP and a biphasic response in AP. All PAF dose response curves were shifted to the right by WEB 2086. Platelet activating factor was a pulmonary hypertensive agent and contributed to the LPS-induced respiratory alterations.

Animals↗
PubMed1991

Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model.

In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or with liposomes alone. After 24 h each animal received an injection of either 10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800) leukocytes per mm3 after injection of 10(10) bacteria. At the same time bacterial clearance was substantially improved by MTP-PE pretreatment. Finally, pretreatment with MTP-PE dramatically reduced mortality; the average death rates for both series of animals used were 55% for liposome-pretreated animals and 3% for animals pretreated with MTP-PE-containing liposomes. These results in a preclinical model suggest that treatment with MTP-PE-containing liposomes might be beneficial in controlling septicemia in patients at risk.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Pharmacokinetics, effect on clotting tests and assessment of the immunogenic potential of hirudin after a single subcutaneous or intravenous bolus administration in man.

The pharmacokinetics and the anticoagulant effects of hirudin were investigated in 12 healthy volunteers after single subcutaneous or intravenous bolus administrations. Hirudin concentrations in citrated plasma and urine were determined with a radioimmunobioassay, which detects the inhibitor by its thrombin-binding capacity. Plasma profiles could be adequately described by the equation for an open two-compartment model (intravenous route) and by the Bateman equation (subcutaneous route), respectively. Within 24 h half of the administered hirudin dose was recovered in the urine in biologically active form. The prolongation of clotting times (activated partial thromboplastin and thrombin time) was dependent on the hirudin plasma concentration. All test subjects tolerated the hirudin injection without visible or measurable side effects. No hirudin-specific antibodies were found after single parenteral administrations.

Biological Assay↗
PubMed1990

Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs.

We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

[Retro- and prospective studies on the value of clinical and laboratory chemical data in acute appendicitis].

In a retrospective study 536 appendicectomized patients were analyzed, in order to identify anamnestic, clinical and laboratory findings which allow the differentiation between acute and non-acute appendicitis. 150 consecutive patients were studied prospectively, which were referred to our department with a presumptive diagnosis of acute appendicitis. Eight single criteria were found, which exhibited a significantly different frequency in acute and non-acute appendicitis. Each criterion showed a low sensitivity and specificity; a score, which was created by combination of these single criteria also had low sensitivity and specificity. We conclude that the correct indication for appendicectomy highly depends on clinical experience of the surgeon.

Acute Disease↗
PubMed1990

[New bone formation following implantation of various hydroxyapatite ceramics. Animal experiment with bore hole models of the sheep tibia].

The aim of this study was to measure new bone formation after implantation of hydroxylapatite ceramic materials compared with autogenous and allogenous cancellous bone implantations. Eight standardised bore holes, each 6 mm in diameter, were drilled in the left medial tibia of each of seven merino sheep. Seven of these holes were filled with hydroxylapatite ceramic materials: Bio-Oss, Pyrost, autogenous and deep frozen allogenous spongiosa in various sequences. The empty hole was used for comparison. Results were evaluated after fluorescent marking with calcein green 6 weeks postoperatively. The extent of new bone formation was determined by means of fluorescence microscopy, microradiography and histological sections and quantified by means of an automatic surface-measuring programme. Whilst implantation of autogenous spongiosa resulted in almost complete slicing of the defect, the holes filled with hydroxylapatite ceramic materials showed no significant difference from the empty defect. We conclude that this purely inorganic material cannot stimulate new bone formation.

Animals↗
PubMed1989

The hypotensive response to des-Arg9-bradykinin increases during E. coli septicemia in the pig.

The sensitivity to des-Arg9-bradykinin of the cardiovascular system was largely increased in piglets with E. coli bacteremia. However, the sensitivity to bradykinin was unchanged under the same condition. These findings indicate the appearance of the kinin B1-receptor in the systemic circulation of the pig during septicemia. Bradykinin induced responses suggest a stable effect mediated by the classical B2-receptor.

Animals↗
PubMed1989

Inhibition of proteinases with recombinant eglin C during experimental Escherichia coli septicemia in the pig.

Administration of the proteinase inhibitor eglin C reduces the symptoms of capillary leakage in a porcine model of septic shock. This was assessed by measurements of blood pressure, plasma protein concentration, hematocrit, and duration of urine production. Eglin C plasma levels around 1.2 microM resulted from a dose of 1.9 mg.kg-1.h-1 for 4 h and were therapeutically effective. A higher dose of eglin C (7.7 mg.kg-1.h-1 for 4 h) induced levels of approximately 5.6 microM in plasma and was not superior. This observation indicates that lysosomal proteases from neutrophils or degranulation of mast cells play a crucial role in the increase of capillary permeability during septicemia.

Animals↗
PubMed1989

The impact of splenectomy on antibody response in the porcine model.

Some controversy exists regarding the antibody response after splenectomy and spleen preserving operations. In a porcine model the specific IgG antibody response to tetanus toxoid and type 6B pneumococcal polysaccharide was studied in 10 animals with splenectomy, 11 animals with splenic resection, 10 animals with splenic autotransplantation and 10 sham operated control animals. The operative groups were divided in two subgroups, receiving either the immuno adjuvant MTP-PE or the vehicle alone. Specific antibodies were determined by ELISA. Immunization with tetanus toxoid led to slightly lower peak IgG levels in splenectomized animals, but this was statistically not significant as compared to controls. In addition, the distribution of responders (78%) was not influenced by type of operation. Type 6B-pneumococcal polysaccharide proved to be a weak immunogen (19% responders). Splenectomy or spleen preserving surgery had no impact on the proportion of responders and peak IgG antibody titers of responders to this antigen. Additional administration of MTP-PE did not significantly increase the proportion of responders and had no impact on peak IgG antibody levels to tetanus toxoid and type 6B pneumococcal polysaccharide. These results show in contrast to previous studies in man, that under controlled conditions in the porcine model serum antibody responses to T-cell dependent and T-cell independent antigens are only slightly decreased by splenectomy. In addition, no effects of spleen preserving operations on antibody response are observed, and there is no change after concomitant administration of a muramyl peptide.

Acetylmuramyl-Alanyl-Isoglutamine↗