Biomedical subjects

R Stocker

Publications and source records attributed to R Stocker.

At least 127 records · Page 7Linked to original sources

PubMed1996

[Percutaneous tracheostomy: a minimally invasive procedure on the intensive care unit].

INTRODUCTION: In 1985 Ciaglia [2] introduced percutaneous tracheostomy as a minimal invasive procedure. Since October 1991 percutaneous tracheostomy has been performed in 40 patients at the University Hospital in Zürich. This paper compares our complication rate using the Cook-system with the conventional open technique in the literature. MATERIALS AND METHODS: 40 patients, mean 53.6 years of age, 26 male, 14 female. Indications were: inability to perform sufficient bronchial suction, recurrent atelectasis, long term ventilation, difficult or prolonged weaning (i.e. neurotrauma). The tracheal tube is introduced following stepwise dilatation after making skin incision, according to the Seldinger technique. RESULTS: In all patients tracheostomy was carried out as an elective procedure in the Intensive Care Unit. Time between primary intubation and tracheostomy varied between O and 51 days, mean 15.9 days. Complications occurred in 5/40 cases (12.5%), with only one serious complication: the tracheostoma was misplaced, requiring intubation. Beside that we have seen 2 minor hematomas, 1 bradycardia and 1 subcutaneous emphysema. CONCLUSIONS: Percutaneous tracheostomy can be safely performed at bedside in the ICU. The method is simple and has a lower complication rate compared to the conventional open technique as reported by Hazard [7] and Griggs [8].

Adult↗

PubMed1996

A rapid and simple screening test for potential inhibitors of tocopherol-mediated peroxidation of LDL lipids.

We report a rapid and convenient method for screening potential inhibitors of the initiation of low density lipoprotein (LDL) lipid peroxidation. The method uses positively and negatively charged micelles of either cetyltrimethyl ammonium chloride or sodium dodecyl sulfate with added alpha-tocopherol. It is based on the capacity of an antioxidant to attenuate alpha-tocopheroxyl radicals, generated by irradiation of the alpha-tocopherol-containing micelles with UV light, and measured directly by electron spin resonance spectroscopy. To establish the reliability of the method, we compared the alpha-to-copheroxyl radical attenuating ability (TRAA) of 53 natural and synthetic potential antioxidants with their respective ability to inhibit the early stages of LDL lipid peroxidation initiated by a low flux of water-soluble peroxyl radicals. The relationship between the measured TRAA and corresponding LDL antioxidation activity was highly significant (P < 0.00005, Rank test). Thus, the potency of a co-antioxidant for LDLs alpha-tocopherol could be predicted with > 98% probability by the TRAA test alone. The results suggest that this relatively simple method represents an effective and simple screening test that can be used for large numbers of potential inhibitors of the early stages of LDL lipid oxidation.

Adult↗

PubMed1996

Oxidation of LDL by recombinant human 15-lipoxygenase: evidence for alpha-tocopherol-dependent oxidation of esterified core and surface lipids.

Various lipoxygenases (LO) oxidize low density lipoprotein (LDL) in vitro and 15-LO has been implicated in the development of atherosclerosis in vivo. Direct oxidation of phospholipids (PL) and cholesteryl esters (CE) by LO has been proposed as a mechanism whereby these enzymes cause or contribute to LDL lipid peroxidation. Herein we show that the extent to which recombinant human 15-LO (rhLO) caused peroxidation of LDL's esterified core and surface lipids depended on, and directly related to, the alpha-tocopherol (alpha-TOH) content of the lipoprotein. Thus, CE and PL of in vivo alpha-TOH-depleted LDL, isolated from a patient with familial isolated vitamin E deficiency, were resistant to oxidation by rhLO, whereas those in alpha-TOH-containing LDL from the same patient receiving vitamin E supplements readily oxidized. The extent to which rhLO caused oxidation of CE and PL directly and linearly correlated with LDL's content of vitamin E, as demonstrated by studies with in vitro alpha-TOH-depleted lipoproteins. The geometric isomers of oxidized cholesteryl linoleate formed in LDL during oxidation initiated by rhLO, matched those obtained during non-enzymic, peroxyl radical-initiated oxidation of LDL whilst alpha-TOH was present. Ascorbate, an efficient co-antioxidant for alpha-TOH, completely prevented rhLO-initiated oxidation of LDL's CE, but did not inhibit rhLO-mediated oxidation of unesterified linoleate. These results are inconsistent with direct oxidation of LDL esterified lipids by rhLO. Isolated LDL contained free fatty acids (FFA), and its exposure to rhLO caused a rapid formation of linoleate hydroperoxide. To reconcile these data, we propose that during rhLO-initiated oxidation of LDL, enzymic oxidation of FFA preceeds the oxidation of CE and PL, which occurs largely via a tocopherol-dependent process.

Arachidonate 15-Lipoxygenase↗

PubMed1995

Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein (LDL): a simple test for tocopherol-mediated peroxidation of LDL lipids.

alpha-Tocopherol (alpha-TOH) can act as a pro- or antioxidant for isolated ubiquinol-10-free human low density lipoprotein (LDL). We demonstrate that alpha-TOH is a more potent pro-oxidant than other forms of vitamin E for LDL peroxidation initiated by mild fluxes of aqueous peroxyl radicals and low concentrations of Cu2+. A simple deuterium exchange test shows that alpha-TOH switches from pro- to anti-oxidant at Cu2+:LDL ratios > 2.5. The results suggest that this test may be useful to distinguish 'inhibited' peroxidation of emulsion lipids propagated via the lipid peroxyl radical from that mediated via the antioxidant radical.

Adult↗

PubMed1995

[Isolated lung transplantation--evaluation of patients and initial results].

Between November 1992 and May 1994 we performed 10 single and 5 double lung transplants in patients with end-stage lung diseases due to lymphangioleiomyomatosis (4), cystic fibrosis (3), pulmonary hypertension (3), pulmonary fibrosis (3) and chronic obstructive lung disease (2). In the 13 patients (87%) surviving for median 245 (19-567) days, FEV1 improved from median 640 ml to 1410 ml and the 12-minute walk distance from median 315 to 1100 meters. 10 patients (77%) enjoy a good or even excellent quality of life. 2 patients died 11 and 62 days postoperatively, due to multi-organ failure and invasive pulmonary aspergillosis respectively. The main postoperative problems are fungal and cytomegalovirus infections and chronic rejection in the form of bronchiolitis obliterans. In Switzerland as elsewhere, lung transplantation has become an established modality for the management of end-stage diseases of the lung and pulmonary circulation.

Adolescent↗

PubMed1995

Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein.

Oxidation of low density lipoprotein (LDL) may be involved in the development of atherosclerosis. It has recently been shown that alpha-tocopherol (alpha-TOH) can act either as an antioxidant or prooxidant for isolated low density lipoprotein (LDL). In the absence of an effective co-antioxidant, alpha-TOH is a prooxidant and this activity is evidently due to reaction of the alpha-tocopheroxyl radical (alpha-TO.) with the LDL's polyunsaturated lipids (Bowry, V. B., and Stocker, R. (1993) J. Am. Chem. Soc. 115, 6029-6045). Herein we examined the effectiveness of selected natural and synthetic radical scavengers as co-antioxidants for inhibiting peroxyl radical-induced peroxidation in LDL that is devoid of ubiquinol-10 (an effective endogenous co-antioxidant) but still contains most of its natural complement of alpha-TOH. Various quinols, catechols, and aminophenols, as well as ascorbate, 6-palmityl ascorbate, and bilirubin, were very effective co-antioxidants under our test conditions, whereas ordinary phenolic antioxidants, including short-tailed alpha-TOH homologues, were less effective. Reduced glutathione, urate, and Probucol were ineffective. These findings confirm that the prooxidant activity of alpha-TOH in LDL relies heavily on the segregation of water-insoluble radicals (particularly alpha-TO.) into individual LDL particles, since it was those compounds that are expected to either irreversibly reduce alpha-TO. or accelerate the diffusion of radicals between particles which most effectively inhibited the tocopherol-mediated phase of peroxidation. Theoretical and practical implications of these findings are discussed, as is their relevance to the "LDL oxidation" hypothesis of atherogenesis.

Bilirubin↗

PubMed1995

[Isolated lung transplantation].

Over the last 10 years, single and bilateral lung transplantation has developed from an experimental technique to a valid therapy for patients with end-stage pulmonary or pulmonary-vascular disease. The main reasons for this progress are better defined selection criteria, improved operative technique and organ preservation, optimized peri- and postoperative management and more precise immunosuppressive and antiinfective therapy. Since 1983 more than 3000 lung transplantations have been performed worldwide with a 1- and 3-year survival rate of 70-90% and 60-70% respectively. In Switzerland 41 lung transplantations have been performed since 1992 with a 1-year survival rate of more than 80%. Indications, technique, treatment and results are discussed.

Adult↗

PubMed1995

[An unusual case of gunshot wound to the head].

We are going to present a special case of head injury caused by a gunshot. In this case it resulted in a fracture of the skull, but the bullet did not penetrate the skull. It was deflected by the bone, leaving the body at an angle. But bone fragments, acting as secondary bullets, penetrated the brain. In spite of a massive cerebral trauma and brain injury, no retrograde amnesia could be diagnosed. The patient recovered to such an extent, that he could return to his former job. Special characteristics of head injuries caused by bullets will be referred to.

Adult↗

PubMed1995

Cholesterylester hydroperoxide reducing activity associated with isolated high- and low-density lipoproteins.

Exposure of isolated high-(HDL) and low-density lipoproteins (LDL) to aqueous peroxyl radicals generated from a thermo-labile azo-compound resulted in immediate formation of cholesteryllinoleate hydroxide (Ch18:2-OH) in addition to hydroperoxides of cholesteryllinoleate (Ch18:2-OOH) and phospholipids. Ch18:2-OH was also formed in peroxyl radical-oxidizing human plasma devoid of ascorbate or low molecular weight compounds or isolated lipoproteins in the presence of desferrioxamine. In contrast, peroxyl radical-mediated oxidation of HDL or LDL lipid extracts or detergent-solubilized lipoproteins resulted in the formation of Ch18:2-OOH without concomitant formation of Ch18:2-OH. Heat treatment of the isolated lipoproteins prior to oxidation greatly reduced Ch18:2-OH formation. Compared to the concentrations of Ch18:2-OOH accumulating, formation of Ch18:2-OH was more pronounced in oxidizing HDL than LDL isolated from the same blood donor. The levels of Ch18:2-OH detected after prolonged oxidation periods were independent of the radical flux to which the lipoproteins were exposed. In the absence of peroxyl radical generator, [3H]Ch18:2-OOH associated with HDL was converted readily and in a biphasic manner into [3H]Ch18:2-OH upon incubation at 37 but not 4 degrees C. LDL-associated [3H]Ch18:2-OOH were also reduced, albeit with an initial reaction rate approximately 10 times slower than that observed with labelled HDL. Together, the results show that cholesterylester hydroxides are formed during (peroxyl) radical-mediated oxidation of isolated intact HDL and LDL under transition metal-free conditions. The findings suggest the presence of a hydroperoxide reducing activity in isolated human lipoproteins, particularly HDL.

Cholesterol Esters↗

PubMed1995

Vitamin C redox reactions in blood of normal and malaria-infected mice studied with isoascorbate as a nonisotopic marker.

It has been suggested that the host antimalarial response depends in part on phagocyte-derived oxidants and that the parasite itself exerts an oxidative stress on its erythrocytic environment. Intraerythrocytic malaria parasites are particularly susceptible to being damaged by oxidative drugs, several of which are under development as chemotherapeutic agents. Thus the antioxidant status and associated regulatory mechanisms of the blood during malaria infection are of great interest. The important antioxidant ascorbate (AH-) and isoascorbate (IAH-), an isomer that does not occur naturally in animals, were found to have similar redox properties. We therefore assessed the usefulness of IAH- as a marker for studies of AH- handling in vivo and in vitro under normal conditions and in murine malaria infection. DHIA added to whole blood from normal or Plasmodium vinckei-infected mice in vitro was rapidly taken up into blood cells and reduced to IAH-. Intracellular IAH- derived from the exogenous DHIA was released into the plasma by blood cells from malaria-infected mice but not those from normal mice. Uptake and reduction of DHIA had no effect on plasma or cellular levels of AH- under these conditions. IAH- injected i.v. into either normal or P. vinckei-infected mice was rapidly cleared in both cases and led to an increase in plasma levels of AH-; this suggested displacement of the latter from some intracellular site, presumably not associated with blood cells. DHIA administered as an intravascular bolus into either normal or malaria-infected mice was rapidly reduced. However, in contrast to the in vitro situation, the concentration of plasma IAH- derived from the injected DHIA was approximately the same in both the infected and control animals. The IAH- so formed disappeared quickly from the plasma. Intravenous injection of DHIA into malaria-infected mice caused a rapid, prolonged increase in the proportion of plasma vitamin C in the form of DHA, whereas in uninfected mice there was a transient decrease in plasma DHA followed by normalisation. The changes in plasma AH- and DHA following IV injection of a single dose of DHA closely paralleled those seen after DHIA administration. These observations indicate that: (i) blood cells from normal and malaria-infected mice take up and reduce DHIA in a similar fashion, but they have different ways of handling the resulting IAH-; (ii) cells other than blood cells are important in the reduction of plasma DHIA and DHA in vivo; (iii) malaria-infected mice are less capable of handling oxidative challenge than normal ones; (iv) in some circumstances IAH- and DHIA may be useful nonisotopic markers for studies of vitamin C handling in vitro and in vivo.

Animals↗

PubMed1995

Is alpha-tocopherol a reservoir for alpha-tocopheryl hydroquinone?

The products of oxidation of the alpha-tocopherol model compound, 2,2,5,7,8-pentamethyl-6-chromanol (PH) by t-butyl hydroperoxide in chloroform varied with the amount of water present. In the presence of a trace of water, the main products were the spirodimer (PSD) and spirotrimer (PST). As the content of water increased, the main product became 2-(3-hydroxy-3-methylbutyl)-3,5,6-trimethyl-1,4-benzoquinone (PQ). Oxidation of PH in aqueous liposome suspension also produced PQ as the major product. These results suggested that, in aqueous solutions, the major oxidation product of PH would be PQ and of alpha-tocopherol (TH) would be alpha-tocopheryl quinone (TQ). The ease of reduction of PQ and TQ was studied in chemical and biological systems. PQ, TQ, and ubiquinone-10 (UQ) were rapidly reduced to their respective hydroquinones (PQH2, TQH2, and UQH2) at pH 7.3 by NADH plus FAD. Whole blood reduced PQ rapidly at 37 degrees C to PQH2 but did not reduce TQ to TQH2. Human peripheral blood mononuclear cells took up TQ from a bovine serum albumin complex and reduced it to TQH2. Ingestion of TQ (350 mg) by one of us (PSK) resulted in the formation of TQH2 during a 5 h period. These results demonstrate that several biological systems are able to reduce TQ to TQH2 and that it is a reaction that may occur normally in vivo.

Blood↗

PubMed1995

Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feeding.

Vitamin E can be a prooxidant in isolated lipoprotein suspensions. Because lipid emulsions used in parenteral nutrition are lipoprotein-like suspensions rich in polyunsaturated fatty acids and vitamin E, we hypothesized that vitamin E may act as a prooxidant in lipid emulsions, as it is in lipoprotein suspensions. We therefore exposed an intravenously administered lipid emulsion (Intralipid) to a single spotlight commonly used in the treatment of neonatal jaundice, and measured the formation of triglyceride hydroperoxides by using high-performance liquid chromatography with postcolumn chemiluminescence detection. Concentrations of these hydroperoxides in different batches of fresh intralipid were usually approximately 10 mumol/L but increased up to 60 times after exposure to phototherapy light for a period of 24 hours, even though significant amounts of vitamin E were present at the end of the exposure. Triglyceride hydroperoxides were formed during phototherapy light exposure whether the intralipid was in plastic tubing used routinely for infusion or in glass containers. Ambient light also caused significant peroxidation of the formula lipids, although to a much lesser extent than observed with phototherapy light. For infants in the neonatal intensive care unit who were receiving intralipid but not phototherapy, solutions being infused at the end of 24 hours contained a mean of 40 mumol/L hydroperoxides. For infants receiving phototherapy, the mean was 97 mumol/L. Phototherapy light-induced formation of triglyceride hydroperoxides was prevented by covering the intralipid with aluminum foil or supplementation with sodium ascorbate before light exposure. We conclude that intralipid is highly susceptible to oxidation and that elevated levels of oxidized lipids can be formed during its clinical use, especially when intralipid infusion is combined with phototherapy. Because lipid hydroperoxides are cytotoxic and can cause adverse effects, inadvertent infusion of rancid intralipid may add to the numerous problems encountered by premature neonates.

Aluminum↗

PubMed1995

Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein.

The oxidation of low-density lipoproteins (LDLs) is now commonly implicated as an important early event in atherogenesis. The resulting interest in LDL antioxidation has focused on alpha-tocopherol, the biologically and chemically most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. We review advances made in our understanding of the molecular action of alpha-tocopherol in radical-mediated oxidation of isolated human LDL and how the vitamin's antioxidant activity is enhanced or even dependent on the presence of suitable reducing species, which are referred to as coantioxidants.

3-Hydroxyanthranilic Acid↗

PubMed1995

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Acute-Phase Proteins↗

PubMed1995

Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha-tocopherol and ascorbate.

We assessed the antioxidant status and contents of unoxidized and oxidized lipids in freshly obtained, homogenized samples of both normal human iliac arteries and carotid and femoral atherosclerotic plaque. Optimal sample preparation involved homogenization of human atherosclerotic plaque for 5 minutes, which resulted in recovery of most of the unoxidized and oxidized lipids without substantial destruction of endogenous vitamins C and E and 87% and 43% recoveries of added standards of alpha-tocotrienol and isoascorbate, respectively. The total protein, lipid, and antioxidant levels obtained from human plaque varied among donors, although the reproducibility of replicates from a single sample was within 3%, except for ubiquinone-10 and ascorbate, which varied by 20% and 25%, respectively. Plaque samples contained significantly more ascorbate and urate than control arteries, with no discernible difference in the vitamin C redox status between plaque and control materials. The concentrations of alpha-tocopherol and ubiquinone-10 were comparable in plaque samples and control arteries. However, approximately 9 mol percent of plaque alpha-tocopherol was present as alpha-tocopherylquinone, whereas this oxidation product of vitamin E was not detectable in control arteries. Coenzyme Q10 in plaque and control arteries was only detected in the oxidized form ubiquinone-10, although coenzyme Q10 oxidation may have occurred during processing. The most abundant of all studied lipids in plaque samples was free cholesterol, followed by cholesteryl oleate and cholesteryl linoleate (Ch18:2). Approximately 30% of plaque Ch18:2 was oxidized, with 17%, 12%, and 1% present as fatty acyl hydroxides, ketones, and hydroperoxides, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Immunologic detection and measurement of hypochlorite-modified LDL with specific monoclonal antibodies.

Oxidation of LDL is thought to contribute to the early stages of atherogenesis. Because myeloperoxidase is present in atherosclerotic lesions and can produce the strong oxidant hypochlorous acid (HOCl), which converts LDL into its high-uptake atherogenic form in vitro, we raised polyclonal and monoclonal antibodies (MoAbs) against HOCl-modified LDL (HOCl-LDL). Characterization of the polyclonal anti-human HOCl-LDL Abs showed that they cross-reacted strongly with 4-hydroxynonenal-, malondialdehyde-, and Cu(2+)-oxidized LDL. Similarly, polyclonal and some monoclonal Abs against aldehyde- and Cu(2+)-modified LDL cross-reacted with HOCl-LDL. In contrast to the polyclonal Abs, two selected hybridoma cell line supernatants containing MoAbs raised against HOCl-LDL (MoAb-A and MoAb-B) did not cross-react with either native LDL or aldehyde- or Cu(2+)-modified LDL. MoAb-A (clone 1B10A11, subtype IgG1 kappa) recognized an epitope that appeared to be specific for HOCl-LDL and depended on the tertiary structure of the (lipo)protein, as judged by a lack of cross-reactivity with HOCl-modified human and bovine serum albumin and a loss of reactivity associated with lipoprotein denaturation. MoAb-B (clone 2D10G9, subtype IgG2b kappa), on the other hand, gave identical titration curves with HOCl-LDL and HOCl-modified albumins, suggesting that this antibody recognized epitopes that are commonly generated on proteins that have been oxidized with HOCl. Thus, MoAb-A and MoAb-B may be useful tools for the investigation of a possible role for HOCl-mediated damage to (lipo)proteins in atherosclerosis and other inflammatory diseases.

Aldehydes↗

PubMed1995

Modulation of superoxide generation in in vivo lipopolysaccharide-primed rat alveolar macrophages by arachidonic acid and inhibitors of protein kinase C, phospholipase A2, protein serine-threonine phosphatase(s), protein tyrosine kinase(s) and phosphatase(s).

Ninety minutes after i.v. injection of Escherichia coli lipopolysaccharide (LPS) (1 mg/kg) into rats, phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide anion (O2-) secretion was enhanced in suspensions of in vivo LPS-treated alveolar macrophages (AM phi) when compared with saline (SAL)-treated AM phi. The purpose of this investigation was to dissect the in vitro mechanism of PMA-stimulated O2- generation in both LPS and SAL-treated rat AM phi, with a panel of inhibitors of protein kinase C (PKC), protein serine-threonine phosphatase(s) (PSP), protein tyrosine kinase(s) (PTK) and phosphatase(s) (PTP), phospholipase A2 (PLA2), cyclooxygenase (CO) and 5-lipoxygenase (5-LO). The following agents blocked PMA-stimulated O2- generation in both LPS- and SAL-treated AM phi (expressed as percentage of control): 1) PKC inhibitors: staurosporine: 100 nM, 7.0% (LPS) and 5.6% (SAL); sphingosine: 10 microM, 21% (LPS) and 10.5% (SAL); 2) PTK inhibitor: genistein: 100 microM, 44% (LPS) and 31% (SAL); 3) PTP inhibitors: phenylarsine oxide, 10 microM, 12.1% (LPS) and 18% (SAL); diamide, 1000 microM, 10.1% (LPS) and 10.5% (SAL); and 4) PLA2 inhibitors: manoalide: 1 microM, 29.3% (LPS) and 5.2% (SAL); scalaradial: 1 microM, 7.7% (LPS) and 7.1% (SAL); and WAY 125,984: 10 microM, 17.1% (LPS) and 14.5% (SAL). In addition, it was observed that exogenously added arachidonic acid (AA)-stimulated O2- generation in a time- and dose-dependent manner in both LPS and SAL-treated AM phi. The following inhibitors enhanced or did not affect PMA-stimulated O2- generation in LPS- and SAL-treated AM phi (expressed as percentage of of control): 1) PSP inhibitors: okadaic acid: 0.5 microM, 117% (LPS) and 153% (SAL); calyculin A: 1 microM, 112% (LPS) and 101% (SAL); 2) CO and 5-LO inhibitors: indomethacin: 10 microM, 107% (LPS) and 90% (SAL); WY 50, 295: 1 microM, 99% (LPS) and 103% (SAL); and 3) the PTP inhibitor orthovanadate upon prolonged preincubation. In both in vivo LPS- or SAL-primed AM phi, PMA-stimulated O2- generation appears to be modulated by PKC, PLA2, AA, PTK, PTP and PSP. No modulatory role was evident for either CO or 5-LO metabolites. These findings might bear on the design of therapeutic approaches for the modulation of O2- release by AM phi in the early stages of sepsis and adult respiratory distress syndrome.

Animals↗

PubMed1995

[Results of surgical management of distal femur fractures with joint involvement].

Results of the treatment of 60 intraarticular distal fractures of the femur (AO classification: 33-B and 33-C fractures) are summarized. Frequencies of the different types of fractures were B1, 7; B2, 10; B3, 4; C1, 10; C2, 1; C3, 8. In 36 patients an isolated fracture, was present, in 9 patients, one additional injury, and in 16 patients there was more than one fracture or multiple trauma. We found 16.7% open fractures. Operation was possible within 24 h in 16 patients, in 21 patients between the 2nd and the 5th days, and in the rest after the 5th day. Check-ups took place an average of 46.4 months after the accident. The average age of the patients was 64.1 years (16-93). We encountered 3 cases of infection; we were able to treat 2 of these successfully, while 1 led to chronic osteomyelitis. Further complications were: loosening of implants (6 cases), non-union (1) fractures of plates (2), haematoma requiring operative treatment (1) refracture (1). All fractures resulted in osseous consolidation. Mobilization of patients was achieved an average of 12 days after operation. We evaluated the cases according to the Neer score. In 32 cases the result was excellent, in 18, average and in 4, unsatisfactory. Failure had to be recorded in 1 case. The combination of locking nails and lagscrews is an alternative method of osteosynthesis for distal femural fractures with an intra-articular component, provided strict selection criteria are applied.

Adolescent↗