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Biomedical subjects

W Seeger

Publications and source records attributed to W Seeger.

At least 19 recordsLinked to original sources
PubMed1992

Experience with the infratentorial supracerebellar approach in lesions of the quadrigeminal region, posterior third ventricle, culmen cerebelli, and cerebellar peduncle.

We report about our experience with the infratentorial supracerebellar approach in 23 patients operated on for lesions located in the posterior part of the third ventricle, quadrigeminal plate, culmen cerebelli and cerebellar peduncle. Three patients had transient worsening of their deficits immediately after surgery. Three patients developed haemorrhages postoperatively requiring surgical evacuation. One of them died. None of the patients developed specific complications which could without any doubt be attributed to the approach. We concluded that in combination with intra-operative CSF drainage and the sitting position the infratentorial supracerebellar approach allows safe access to lesions situated in an area limited by the posterior part of the third ventricle, the fastigium level and both cerebellar peduncles.

Adolescent↗
PubMed1992

Surfactant protein A (SP-A) is decreased in acute parenchymal lung injury associated with polytrauma.

To further investigate if the pulmonary surfactant system is altered in acute parenchymal lung injury of adults following polytrauma we measured SP-A level and phospholipid composition in 150 sequentially obtained lung lavage samples from poly-traumatized patients (n = 19) beginning at the day of trauma and ending 18 days later or when the patient was extubated. Out of the 19 patients studied 10 had severe parenchymal lung injury (ARDS), nine had moderate lung injury. SP-A was measured using a two-monoclonal sandwich ELISA-assay. Phospholipids were separated using high-performance liquid chromatography and their composition was calculated by comparison with standard phospholipid mixtures. We found immunoreactive SP-A concentrations ranging from 0.1 micrograms ml-1 to 8.5 micrograms ml-1 lung lavage fluid obtained from all patients. The mean SP-A concentration in patients who had severe parenchymal lung injury (ARDS) was 1.06 +/- 0.16 micrograms ml-1 lavage fluid, the mean concentration in patients who had only moderate parenchymal lung injury was 1.92 +/- 0.18 micrograms ml-1 lavage fluid. Both concentrations were lower than in healthy controls (2.74 +/- 0.3 micrograms ml-1 lavage fluid; n = 12). In patients who had moderate lung injury the SP-A level normalized, but in patients who had severe lung injury the SP-A level remained low during the timespan examined. SP-A alterations did not correlate to changes in phospholipid composition as determined in lung lavage samples of individual patients. We conclude that alveolar SP-A concentrations decrease in polytraumatized patients who have acute parenchymal lung injury soon after the trauma occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Differential sensitivity to fibrinogen inhibition of SP-C- vs. SP-B-based surfactants.

Inhibition of surfactant function by plasma-derived proteins is assumed to occur under conditions of alveolar protein leakage. We investigated surface properties and sensitivity to the inhibitory capacity of fibrinogen (Fbg) of artificial surfactants in a pulsating-bubble surfactometer. Phospholipid-fatty acid mixtures (PLM) with or without hydrophobic apoproteins [natural bovine surfactant proteins (SP) B and C, recombinant human SP-C] were used. Without Fbg, all apoprotein-based surfactants exhibited rapid absorption facilities and reduced surface tension to near zero values under dynamic compression. Fbg caused a dose-dependent reduction of adsorption kinetics and dynamic surface tension-lowering properties of all surfactant preparations, but there was a marked rank order of "Fbg sensitivity": PLM without apoprotein being the most sensitive and SP-B-based PLM the least. Fbg sensitivity of recombinant SP-C-based PLM could be lowered dose dependently by adding small amounts of SP-B. For further support of a putative role of SP-B in resistance to Fbg inhibition, calf lung surfactant extract was incubated with monoclonal antibody against SP-B. Without Fbg, anti-SP-B had little influence. However, sensitivity to the inhibitory effect of Fbg was markedly and dose dependently increased by anti-SP-B but not by control immunoglobulin. We conclude that SP-B-based surfactant preparations display markedly lower susceptibility to Fbg inhibition than SP-C combinants.

Adsorption↗
PubMed1992

Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs.

The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.

Animals↗
PubMed1992

Type II alveolar epithelial eicosanoid metabolism: predominance of cyclooxygenase pathways and transcellular lipoxygenase metabolism in co-culture with neutrophils.

Arachidonic acid (AA) metabolism was studied in freshly isolated type II alveolar epithelial cells of rabbits. Substantial basal secretion of prostanoids with predominance of prostaglandin (PG) I2 was noted. Challenge with the calcium ionophore A23187 resulted in a time- and dose-dependent increase in the generation of all AA cyclooxygenase products to severalfold values following the rank order of 12-heptadecatrienoic acid (12-HHT) greater than PGI2 greater than PGE2 greater than or equal to thromboxane A2 greater than PGF2 alpha approximately PGD2. Even larger augmentation of prostanoid generation was evoked by challenge with free exogenous AA. Generation of the different AA cyclooxygenase products was inhibited by acetylsalicylic acid with IC50 in the range between 250 and 500 microM. In addition to the prostanoid release, ionophore-challenged type II pneumocytes liberated substantial amounts of AA lipoxygenase products with leukotriene (LT) B4 greater than 15-hydroxyeicosatetraenoic acid (HETE) greater than 12-HETE greater than 5-HETE. Generation of LTs and HETEs was markedly increased upon simultaneous disposal of free exogenous AA. No omega-oxidation of LTB4 was noted, and no evidence for secretion of intact LTA4 was obtained. The epithelial cells displayed avid uptake of exogenously offered LTA4 with subsequent enzymatic conversion to LTB4. Co-stimulation of pneumocytes with neutrophils (PMN) resulted in an amplification of LTB4 generation, paralleled by a decrease in nonenzymatic decay products of PMN-derived LTA4; both phenomena were dose dependent on the pneumocyte-PMN ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Indications for surgery and prognosis in patients with cerebral cavernous angiomas.

Seventy-three cerebral cavernous angiomas were removed microsurgically from a series of 71 patients between August, 1983 and December, 1989. This retrospective investigation assessed the current indications for surgery and determined the prognosis for patients with cerebral cavernous angioma. There were 38 males and 33 females with a mean age of 37 years. Analysis included clinical presentation and history, neuroradiological findings, indications for surgery, and postoperative course. After an average follow-up period of 15 months, 35 patients were symptom-free, 16 had improved preoperative complaints, six were unchanged, and eight had deteriorated. Microsurgical extirpation of the malformation is indicated in all symptomatic patients where neuroimaging demonstrates the presence of a readily accessible cerebral cavernoma. Surgery is recommended in cases with deep-seated lesions causing massive hemorrhage, repetitive minor bleeding, or significant long-standing and progressive neurological disabilities. Clinically silent cavernomas located in eloquent regions of the brain contraindicate surgery, but should be closely monitored. Patients presenting with convulsions or neurological deficits caused by easily accessible cavernomas of the hemispheres have the best prognosis and a negligible risk for surgical complications. Those with deep-seated lesions of eloquent regions of the brain that have bled or caused sustained neurological disorders face the highest risk for morbidity owing to the surgical intervention, requiring careful preoperative evaluation.

Adolescent↗
PubMed1992

Induction of severe vascular leakage by low doses of Escherichia coli hemolysin in perfused rabbit lungs.

S. aureus alpha-toxin and E. coli hemolysin (Hly) represent two prototypes of pore-forming cytolysins. Both are established virulence factors and have been implicated in the development of septic lung failure. Low doses of these agents cause thromboxane-mediated vasoconstriction and edema formation in isolated perfused rabbit lungs. In a preceding investigation, we observed that alpha-toxin causes overt endothelial cell damage in these lungs, as demonstrable by electron microscopy (Seeger W, Birkemeyer RG, Ermert L, Suttorp N, Bhakdi S, Duncker HR: Lab Invest 63:341, 1990). Here, we present results of a parallel study conducted with E. coli hemolysin. Thromboxane-dependent pulmonary hypertension was suppressed by the addition of acetylsalicylic acid to the perfusion fluid in all cases. Administration of 0.2 hemolytic units (HU; i.e., 20 ng/ml protein) resulted in progressive weight gain after a lag period of 10 to 15 minutes, and 30 minutes after toxin application the gravimetrically determined capillary filtration coefficients (Kfc) were increased greater than 10-fold. Perfusion was terminated when the total lung weight gain surpassed 20 gm. 0.12 HU/ml E. coli hemolysin caused 2- to 3-fold increased capillary filtration coefficients values within 110 minutes, concomitant with intermediate quantities of edema formation (9.7 +/- 2.7 gm). Potassium liberation in the absence of lactate dehydrogenase release occurred in all toxin treated lungs. Electron microscopic examination after perfusion fixation revealed interstitial edema formation in areas remote from the blood-gas exchange barrier. Increased numbers of endothelial plasmalemmal vesicles were visualized at the very onset of edema formation in lungs exposed to 0.2 HU/ml, and after a 110-minute exposure to 0.12 HU/ml of the toxin, but not in lungs exhibiting severe edema (greater than 20 gm weight gain). In contrast to our previous results with alpha-toxin, endothelial cells displayed normal electron density here and were not detached from the fused basal lamina. Hence, although both pore formers provoke severe vascular leakage in our experimental model, the underlying pathways probably divert fundamentally from each other.

Animals↗
PubMed1992

Ligand-operated synthesis of 4-series and 5-series leukotrienes in human neutrophils: critical dependence on exogenous free fatty acid supply.

The influence of exogenously supplied free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the 5-lipoxygenase metabolism in human neutrophils (PMN) was investigated. Simultaneous application of A23187 with incremental concentrations of free AA caused a dose-dependent augmentation of the ionophore-elicited eicosanoid generation [release of leukotriene B4 and its omega-oxidation products, nonenzymatic hydrolysis products of leukotriene A4, and 5-hydroxyeicosatetraeneoic acid (5-HETE)]. A23187 challenge in the presence of free EPA resulted in the dose-dependent appearance of corresponding n - 3-derived metabolites, parallelled by a decrease in 4-series leukotrienes and 5-HETE. The inflammatory ligands formyl-methionyl-leucyl-phenylalanine and platelet-activating factor evoked no substantial eicosanoid generation in the absence of exogenously supplied polyunsaturated fatty acids (PUFAs). Addition of free AA or EPA in parallel with the ligand challenge evoked exclusive and dose-dependent generation of the respective leukotrienes and 5-HETE or 5-hydroxyeicosapentaenoic acid. Total amounts of 5-lipoxygenase products elicited under these conditions approached those in ionophore-stimulated PMN, with platelet-activating factor challenge surpassing the formyl-methionyl-leucylphenylalanine-evoked effect by approximately 50%. Two thirds of the maximum effect was obtained in the presence of only 10 microM free PUFA. Use of labeled fatty acids suggested exclusive origin of the eicosanoids from the exogenously provided precursor PUFA. Critical dependence on timing was noted; maximum response occurred upon simultaneous application of PUFA and ligand, and only 5 min of delay between AA or EPA addition and ligand challenge sufficed to reduce the formation of respective metabolites to less than 20%. EPA competed with AA and was noted to be the preferred substrate for ligand-evoked eicosanoid synthesis. In contrast to the simultaneous addition of free PUFAs, preloading of PMN with AA or EPA for 60 min revealed only very moderate or even no influence on ionophore- or ligand-evoked eicosanoid synthesis. We conclude that inflammatory ligands induce marked stimulation of PMN eicosanoid synthesis, with critical dependence on the presence of free precursor PUFAs. Preference of EPA over AA is observed under these conditions.

Calcimycin↗
PubMed1991

Suppression of cytoskeletal rearrangement in activated human neutrophils by botulinum C2 toxin. Impact on cellular signal transduction.

Botulinum C2 toxin, a binary toxin which selectively ADP-ribosylates nonmuscle G-actin, was used to evaluate the role of cytoskeletal rearrangement in ligand-evoked signal transduction and secretory processes in human neutrophils (polymorphonuclear leukocyte). Preincubation with the combined toxin components reduced the basal F-actin content and nearly completely suppressed the actin assembly initiated by the peptide and lipid chemoattractants formyl-methionyl-leucyl-phenylalanine, platelet activating factor, and leukotriene B4. Superoxide production and elastase secretion were increased markedly under these conditions. Concomitantly, ligand-elicited phosphoinositide hydrolysis was augmented with particular increase in inositol monophosphate. This was paralleled by a severalfold amplification of diacylglycerol formation and sustained elevation of cytosolic calcium. The toxin-effected amplification of postreceptor events and secretory responses was most pronounced in response to formyl-methionyl-leucyl-phenylalanine greater than platelet activating factor greater than leukotriene B4. All metabolic and secretory effects in C2 toxin-pretreated cells were sensitive to pertussis toxin inhibition. In conjunction with the recent finding of unchanged formyl-methionyl-leucyl-phenylalanine receptor binding and dissociation dynamics under influence of C2 (Norgauer, J., Just, I., Aktories, K., and Sklar, L. A. (1989) J. Cell Biol. 109, 1133-1140), the present investigation suggests amplification of postreceptor events as a major mechanism underlying C2 toxin-related increase in polymorphonuclear leukocyte secretory responses. Cytoskeletal rearrangement, putatively linked to phosphoinositide turnover and calcium transients, thus appears to be operative in temporal and/or spatial limitation of chemoattractant-evoked cellular signal transduction.

Actins↗
PubMed1991

Subhemolytic doses of Escherichia coli hemolysin evoke large quantities of lipoxygenase products in human neutrophils.

Polymorphonuclear leukocytes (PMN) have been identified as preferred target cells for Escherichia coli hemolysin in human blood (Bhakdi, S., Greulich, S., Muhly, M., Eberspächer, B., Becker, H., Thiele, A., and Hugo, F. (1989) J. Exp. Med. 169, 737-754). Leukotriene and 5-hydroxyeicosatetraenoic acid generation was investigated in human PMN challenged with E. coli hemolysin in the absence or presence of free arachidonic acid or eicosapentaenoic acid (EPA). In the absence of exogenous free fatty acids, E. coli hemolysin (0.01-10 hemolytic units/ml) induced moderate generation of leukotriene B4 (LTB4) and its omega-oxidation products. The presence of free arachidonic acid (10 microM) during E. coli hemolysin (0.1 hemolytic unit/ml) challenge evoked the generation of large quantities of these products (greater than 100 pmol/1.5 x 10(7) PMN). In parallel, large amounts of 5-hydroxyeicosatetraenoic acid and nonenzymatic LTA4 hydrolysis products appeared. Product release peaked or plateaued 5-10 min after E. coli hemolysin challenge. The presence of exogenous EPA upon E. coli hemolysin challenge resulted in the exclusive generation of LTB5 and metabolites, LTA5 decay products and 5-hydroxyeicosapentaenoic acid. Dose and time dependences corresponded to those with arachidonic acid provision, and the total of EPA-derived products surpassed that of arachidonic acid metabolites in corresponding experiments approximately 2-fold. Increasing the time between free fatty acid provision and E. coli hemolysin challenge resulted in a rapid decline in the generation of arachidonic acid or EPA metabolites. Thus, subhemolytic doses of E. coli hemolysin evoke marked PMN eicosanoid generation that is dependent on exogenous free fatty acid supply, with total amounts approximating those found in calcium ionophore-stimulated neutrophils.

Bacterial Proteins↗
PubMed1991

Surface properties and sensitivity to protein-inhibition of a recombinant apoprotein C-based phospholipid mixture in vitro--comparison to natural surfactant.

Surfactant alterations due to protein leakage are implicated in the pathogenesis of the adult respiratory distress syndrome. In the present study, surface properties of a palmitic acid containing phospholipid mixture (DPPC: PG: PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance and in a pulsating bubble surfactometer. Adsorption facilities and dynamic surface tension-lowering properties of the surfactants alone, their sensitivity to the inhibitory effect of fibrinogen (fbg), and their capacity to restore surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited surface activity, was very sensitive to inhibition by fbg and had moderate effect on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE revealed similar excellent adsorption kinetics and dynamic surface tension lowering properties. Higher percentage of SP-C within the synthetic mixture (up to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%) did not further improve these surface properties. However, PLM-Crec was markedly more sensitive to inactivation by fbg than CLSE. The surface activity of fbg-inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in both the Wilhelmy and the bubble system, with slight superiority of the natural surfactant extract. We conclude that the surface properties of PLM-Crec are clearly superior to those of the apoprotein-free lipid mixture and are similar to those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy in restoring the surface properties of fbg-inhibited CLSE as compared to the natural material.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

Procoagulant activity in bronchoalveolar lavage of severely traumatized patients--relation to the development of acute respiratory distress.

In a prospective study in severely traumatized patients, procoagulant activity (PCA) was determined in bronchoalveolar lavage fluids (BAL). Bronchoscopy with lavage was serially performed during the first 15 days after injury (in total 148 samples of 25 patients). PCA was measured as recalcification times in the absence or presence of excess phosphatidylethanolamine and translated into procoagulant unit equivalents using standard thromboplastin. The data were correlated to the extent of respiratory failure in the injured patients and were compared to PCA in 29 lavage samples obtained from 10 healthy control subjects. A several-fold increase in BAL PCA was noted in all trauma victims, evident already within the first 24 h after injury. A progressive rise in PCA occurred from the 4th posttraumatic day and was highly significantly more pronounced in patients developing serious respiratory failure than in those with only mild pulmonary dysfunction. Significant correlations were noted between PCA increase and alveolar protein-leakage, granulocyte-influx and surfactant alterations, however with correlation coefficients not surpassing 0.55. We conclude that a marked increase in procoagulant activity occurs in severely injured patients, which may favour alveolar fibrin deposition and is related to the development of acute respiratory failure.

Blood Coagulation Factors↗
PubMed1991

Technical improvements in the lateral suboccipital approach for neurovascular decompression of the trigeminal and facial nerves.

Some refinements of the surgical procedure are described in 12 patients (five females, seven males) operated on for neurovascular decompression (ND) in the presence of trigeminal neuralgia and hemifacial spasm. The patients were operated upon in the supine position, in which the use of a lumbar drainage facilitates the dissection from the beginning. The lateral suboccipital approach was performed by means of a semi-osteoplastic craniotomy with the use of bone chips to close the bone defects so that a good cosmetic effect could be achieved.

Adult↗
PubMed1991

Microsurgery of deep-seated cavernous angiomas: report of 26 cases.

The authors review 26 patients with deep-seated cavernous angiomas which were removed by microsurgery. Ten of the angiomas were located in the insula and basal ganglia, 2 in the thalamus, 5 in the midbrain, 8 in the pons, and 1 in the brachium pontis. The patients were among 73 consecutive cases operated on between August 1983 and December 1989 for symptomatic cavernous angiomas in various locations. In 11 cases total excision of the cavernoma was achieved without producing additional neurological deficits. Postoperative neurological recovery was delayed in 7 patients. In the remaining 8, the complicated postoperative course was caused by bleeding from residual parts of the malformation or damage to long-tract pathways in two cases, respectively, vascular injury during dissection in three cases, and paradoxical air embolism in one case. In order to achieve a satisfactory surgical result, it is stressed that particular attention has to be paid to the operative approach, to careful dissection and complete removal of the malformation, to perforating arteries, and to anomalous venous drainage.

Adolescent↗
PubMed1991

High-dose IgG for neutropenic patients with acquired immunodeficiency syndrome (AIDS).

Leukocytopenia and bacterial infections are common and serious complications in patients with AIDS. We report here on three patients in whom the administration of high IgG doses led to gradual (two patients) or prompt (one patient) increases in circulating leukocyte counts (from 200-600 to 2500-5900/microliters), inducing definite improvement in two patients; one patient died from Pneumocystis carinii pneumonia. Although the rise in leukocyte counts lasted for only approximately 3 weeks, high-dose IgG might be a useful therapeutic adjunct in such patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Omega-oxidized leukotriene B4 detected in the broncho-alveolar lavage fluid of patients with non-cardiogenic pulmonary edema, but not in those with cardiogenic edema.

Leukotriene (LT) generation has been implicated in the pathogenesis of the acute respiratory distress syndrome, ARDS. In the present study, we analysed broncho-alveolar lavage fluids of patients on mechanical ventilation because of ARDS (17 samples taken from 9 patients) or because of cardiogenic edema (8 samples taken from 6 patients) and of healthy volunteers (10 samples from different donors). LTs were separated as methylated and non-methylated compounds using different HPLC procedures, and were identified by chromatographic mobility, on-line UV-spectrum analysis and post HPLC immunoreactivity. In the lavage samples of the healthy volunteers and the patients with cardiogenic edema, no LTs were detected by these techniques (detection limit congruent to 0.1-0.2 ng/ml lavage fluid). By contrast, in 15 out of 17 samples from patients with ARDS LTB4 or its metabolites 20-OH-LTB4 and 20-COOH-LTB4 were detected. The endproduct of omega-oxidation, 20-COOH-LTB4, represented the quantitatively predominant compound, detected in the range of 0.3-2.6 ng/ml perfusate. We conclude that the chemotactic agent LTB4 may be involved in the amplification of inflammatory events encountered in ARDS, and that the oxidized metabolites of LTB4 are particularly suitable for monitoring lung leukotriene generation under conditions of neutrophil efflux and oxidative stress.

Adult↗