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R Stocker

Publications and source records attributed to R Stocker.

At least 37 records · Page 2Linked to original sources
PubMed2000

Myeloperoxidase binds to low-density lipoprotein: potential implications for atherosclerosis.

Myeloperoxidase (MPO), an abundant heme enzyme released by activated phagocytes, catalyzes the formation of a number of reactive species that can modify low-density lipoprotein (LDL) to a form that converts macrophages into lipid-laden or 'foam' cells, the hallmark of atherosclerotic lesions. Since MPO has been shown to bind to a number of different cell types, we investigated binding of MPO to LDL. Using the precipitation reagents phosphotungstate or isopropanol, MPO co-precipitated with LDL, retaining its catalytic activity. The association of MPO with LDL was confirmed using native gel electrophoresis. MPO was also found to co-precipitate with apolipoprotein B-100-containing lipoproteins in whole plasma. No precipitation of MPO was observed in lipoprotein-deficient plasma, and there was a dose-dependent increase in precipitation following addition of LDL to lipoprotein-deficient plasma. Binding of MPO to LDL could potentially enhance site-directed oxidation of the lipoprotein and limit scavenging of reactive oxygen species by antioxidants.

Arteriosclerosis↗
PubMed2000

Seroprevalence of diphtheria immunity among injured adults in Austria.

Over a period of 1 year a seroepidemiological study was conducted at the outpatient clinic of a trauma department. Immunity to diphtheria was determined in serum samples from 558 injured patients (205 women and 353 men, age from 18 to 70). Diphtheria-antitoxin concentrations were measured with an enzyme immunoassay and a tissue culture toxin-neutralization assay. Sero-immunity was classified as susceptibility (<0.01 IU/ml), basic protection (0.01-<0.1 IU/ml) and full protection (>/=0.1 IU/ml) against the toxic manifestations of the disease. A total of 27.1% of the subjects were susceptible to diphtheria, 26.5% had basic protection, and 46.4% were fully protected. The median antitoxin concentration reached 0.08 IU/ml (0. 0-0.29; quartiles Q25-Q75). A non linear trend toward decreasing immunity with increasing age was observed (P<0.001) and females proved less protected than males (P=0.006). The country of original immunization (Austria, Western European countries, Eastern European countries and Non European countries) had no influence on sero-immunity (P=0.49). Multiple linear regression analysis revealed that age (P<0.001) and gender (P=0.004) had a significant independent influence on diphtheria immunity level, whereas the country of original immunization was not significant (P=0.72).

Adolescent↗
PubMed2000

[Clinical management of acute head injury].

Patients after acute head injury are susceptible to secondary insults and therefore to secondary brain injury. A comprehensive approach, starting at the site of the accident, followed by emergency diagnosis and treatment in the appropriate emergency department of the trauma centre, intensive care and specific neurorehabilitation is the only way to minimise sequelae of primary brain lesions, prevent secondary brain damage and establish optimum frame conditions with respect to recovery from non-definite brain damage.

Accidents↗
PubMed2000

Oxidation of methionine residues to methionine sulfoxides does not decrease potential antiatherogenic properties of apolipoprotein A-I.

The initial stage of oxidation of high density lipoproteins (HDL) is accompanied by the lipid hydroperoxide-dependent, selective oxidation of two of the three Met residues of apolipoprotein A-I (apoA-I) to Met sulfoxides (Met(O)). Formation of such selectively oxidized apoA-I (i.e. apoA-I(+32)) may affect the antiatherogenic properties of HDL, because it has been suggested that Met(86) and Met(112) are important for cholesterol efflux and Met(148) is involved in the activation of lecithin:cholesterol acyl transferase (LCAT). We therefore determined which Met residues were oxidized in apoA-I(+32) and how such oxidation of apoA-I affects its secondary structure, the affinity for lipids, and its ability to remove lipids from human macrophages. We also assessed the capacity of discoidal reconstituted HDL containing apoA-I(+32) to act as substrate for LCAT, and the dissociation of apoA-I and apoA-I(+32) from reconstituted HDL. Met(86) and Met(112) were present as Met(O), as determined by amino acid sequencing and mass spectrometry of isolated peptides derived from apoA-I(+32). Selective oxidation did not alter the alpha-helicity of lipid-free and lipid-associated apoA-I as assessed by circular dichroism, and the affinity for LCAT was comparable for reconstituted HDL containing apoA-I or apoA-I(+32). Cholesteryl ester transfer protein mediated the dissociation of apoA-I more readily from reconstituted HDL containing apoA-I(+32) than unoxidized apoA-I. Also, compared with native apoA-I, apoA-I(+32) had a 2- to 3-fold greater affinity for lipid (as determined by the rate of clearance of multilamellar phospholipid vesicles) and its ability to cause efflux of [(3)H]cholesterol, [(3)H]phospholipid, and [(14)C]alpha-tocopherol from lipid-laden human monocyte-derived macrophages was significantly enhanced. By contrast, no difference was observed for cholesterol and alpha-tocopherol efflux to lipid-associated apolipoproteins. Together, these results suggest that selective oxidation of Met residues enhances rather than diminishes known antiatherogenic activities of apoA-I, consistent with the overall hypothesis that detoxification of lipid hydroperoxides by HDL is potentially antiatherogenic.

Apolipoprotein A-I↗
PubMed2000

Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis.

The oxidation theory of atherosclerosis proposes that the oxidative modification of low-density lipoproteins (LDL) plays a central role in the disease. Although a direct causative role of LDL oxidation for atherogenesis has not been established, oxidized lipoproteins are detected in atherosclerotic lesions, and in vitro oxidized LDL exhibits putative pro-atherogenic activities. alpha-Tocopherol (alpha-TOH; vitamin E), the major lipid-soluble antioxidant present in lipoproteins, is thought to be antiatherogenic. However, results of vitamin E interventions on atherosclerosis in experimental animals and cardiovascular disease in humans have been inconclusive. Also, recent mechanistic studies demonstrate that the role of alpha-TOH during the early stages of lipoprotein lipid peroxidation is complex and that the vitamin does not act as a chain-breaking antioxidant. In the absence of co-antioxidants, compounds capable of reducing the alpha-TOH radical and exporting the radical from the lipoprotein particle, alpha-TOH exhibits anti- or pro-oxidant activity for lipoprotein lipids depending on the degree of radical flux and reactivity of the oxidant. The model of tocopherol-mediated peroxidation (TMP) explains the complex molecular action of alpha-TOH during lipoprotein lipid peroxidation and antioxidation. This article outlines the salient features of TMP, comments on whether TMP is relevant for in vivo lipoprotein lipid oxidation, and discusses how co-antioxidants may be required to attenuate lipoprotein lipid oxidation in vivo and perhaps atherosclerosis.

Animals↗
PubMed2000

[Intensive care treatment concepts after traumatic spinal cord injury].

Spinal injuries are caused by strong traumatic impacts, followed not only by a local spinal reaction but also systemic involvement. The main problems in the early posttraumatic period are haemodynamic instability, pulmonary insufficiency and SIRS. In this period multiple risks of secondary injuries to the spinal cord or other organs exist and may develop towards life-threatening sepsis, ARDS and multi-organ failure. Optimum therapy for spinal injury patients is demanding and requires an experienced team for diagnosis as well as primary and secondary care. Close cooperation between intensive care and surgery is also important.

Critical Care↗
PubMed2000

Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults.

Oxidative modification of low-density lipoprotein (LDL) may cause arterial endothelial dysfunction in hyperlipidemic subjects. Antioxidants can protect LDL from oxidation and therefore improve endothelial function. Dietary supplementation with coenzyme Q (CoQ(10)) raises its level within LDL, which may subsequently become more resistant to oxidation. Therefore, the aim of this study was to assess whether oral supplementation of CoQ(10) (50 mg three times daily) is effective in reducing ex vivo LDL oxidizability and in improving vascular endothelial function. Twelve nonsmoking healthy adults with hypercholesterolemia (age 34+/-10 years, nine women and three men, total cholesterol 7.4+/-1.1 mmol/l) and endothelial dysfunction (below population mean) at baseline were randomized to receive CoQ(10) or matching placebo in a double-blind crossover study (active/placebo phase 4 weeks, washout 4 weeks). Flow-mediated (FMD, endothelium-dependent) and nitrate-mediated (NMD, smooth muscle-dependent) arterial dilatation were measured by high-resolution ultrasound. CoQ(10) treatment increased plasma CoQ(10) levels from 1.1 +/-0.5 to 5.0+/-2.8 micromol/l (p =.009) but had no significant effect on FMD (4.3+/-2.4 to 5.1+/-3.6 %, p =.99), NMD (21.6+/-6.1 to 20.7+/-7.8 %, p = .38) or serum LDL-cholesterol levels (p = .51). Four subjects were selected randomly for detailed analysis of LDL oxidizability using aqueous peroxyl radicals as the oxidant. In this subgroup, CoQ(10) supplementation significantly increased the time for CoQ(10)H(2) depletion upon oxidant exposure of LDL by 41+/-19 min (p = .04) and decreased the extent of lipid hydroperoxide accumulation after 2 hours by 50+/-37 micromol/l (p =.04). We conclude that dietary supplementation with CoQ(10) decreases ex-vivo LDL oxidizability but has no significant effect on arterial endothelial function in patients with moderate hypercholesterolemia.

Adolescent↗
PubMed2000

Effect on diphtheria immunity of combined tetanus and diphtheria booster vaccination in adults.

The effect of a single booster injection of an adult formulation of a combined diphtheria-tetanus vaccine (Td) on diphtheria-specific immunity was evaluated. The booster injection, containing 2 IU diphtheria toxoid per dose, was given as part of the surgical wound management for adults with open soft tissue injuries. Diphtheria antitoxin concentrations were determined in serum samples from 534 patients (199 women and 335 men, aged 18-70 years) using an enzyme immunoassay and a tissue culture toxin neutralization assay. Seroimmunity against diphtheria toxin was classified at three levels: susceptibility, basic protection, and full protection against the toxic manifestations of the disease. Before vaccination, 27.1% of the subjects were susceptible to diphtheria, 26.5% had basic protection, and 46.4% were fully protected. Six weeks (minimum 25 days, maximum 98 days) after a single booster injection, 89.7% of the subjects achieved full protection against diphtheria, and only 3.9% had antitoxin levels below the protective level. The median increase from the prevaccination to postvaccination antitoxin concentration was found to be 14-fold (4.4-47; quartiles Q25 to Q75). The change in antitoxin levels after revaccination was higher in older age groups (P< 0.001), whereas neither sex (P = 0.86) nor the country of previous immunization with a different national immunization schedule (P=0.61) had a significant influence on the revaccination effect. Systemic adverse reactions were rare, and local reactions of clinical significance were reported in only 1.9% of subjects.

Adolescent↗
PubMed2000

Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect.

OBJECTIVES: To test the hypothesis that antioxidant therapy would improve endothelial function in smokers. BACKGROUND: Several studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known. METHODS: We studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 +/- 6 years, 8 male subjects, 21 +/- 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit. RESULTS: At baseline, plasma ascorbate level was low in the smokers (42 +/- 21 micromol/liter; normal range, 50 to 150 micromol/liter), increased with vitamin C therapy after 2 h to 120 +/- 54 micromol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 +/- 32 micromol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 +/- 2.0% to 6.3 +/- 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 +/- 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout. CONCLUSION: Oral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels.

Administration, Oral↗
PubMed2000

Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice.

Oxidation of low-density lipoprotein (LDL) lipid is implicated in atherogenesis and certain antioxidants inhibit atherosclerosis. Ubiquinol-10 (CoQ10H2) inhibits LDL lipid peroxidation in vitro although it is not known whether such activity occurs in vivo, and, if so, whether this is anti-atherogenic. We therefore tested the effect of ubiquinone-10 (CoQ10) supplemented at 1% (w/w) on aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. Hydroperoxides of cholesteryl esters and triacylglycerols (together referred to as LOOH) and their corresponding alcohols were used as the marker for lipoprotein lipid oxidation. Atherosclerosis was assessed by morphometry at the aortic root, proximal and distal arch, and the descending thoracic and abdominal aorta. Compared to controls, CoQ10-treatment increased plasma coenzyme Q, ascorbate, and the CoQ10H2:CoQ10 + CoQ10H2 ratio, decreased plasma alpha-tocopherol (alpha-TOH), and had no effect on cholesterol and cholesterylester alcohols (CE-OH). Plasma from CoQ10-supplemented mice was more resistant to ex vivo lipid peroxidation. CoQ10 treatment increased aortic coenzyme Q and alpha-TOH and decreased the absolute concentration of LOOH, whereas tissue cholesterol, cholesteryl esters, CE-OH, and LOOH expressed per bisallylic hydrogen-containing lipids were not significantly different. CoQ10-treatment significantly decreased lesion size in the aortic root and the ascending and the descending aorta. Together these data show that CoQ10 decreases the absolute concentration of aortic LOOH and atherosclerosis in apoE-/- mice.

Animals↗
PubMed2000

Total versus tube-related additional work of breathing in ventilator-dependent patients.

BACKGROUND: In tracheally intubated or tracheostomized spontaneously breathing patients, tube resistance can highly increase the patient's work of breathing. In this study we focused upon the relationship between total (WOBtot) and tube-related additional inspiratory work of breathing (WOBadd) and compared different ventilatory modalities for proper tube compensation. METHODS: In ten tracheostomized spontaneously breathing patients we measured WOBtot and WOBadd in the continuous positive airway pressure (CPAP) mode, under inspiratory pressure support of 5, 10, and 15 cmH2O in the pressure support ventilation (PSV) mode, and under flow-adjusted pressure support in the automatic tube compensation (ATC) mode. WOBadd and WOBtot were calculated on the basis of measured tracheal pressure and esophageal pressure, respectively. Inspiratory peak tracheal pressure above PEEP was taken as an estimate of pressure support beyond mere tube compensation (i.e., overcompensation). RESULTS: The percentage of the tube-related WOBadd on WOBtot in the CPAP mode was 52%. It decreased with increasing pressure support in the PSV mode from 32% (PSV 5 cmH2O) to 17% (PSV 15 cmH2O). WOBadd was only 15% of WOBtot in the ATC mode. In contrast to the other ventilatory modes, reduction of WOBadd in the ATC mode was achieved with the smallest amount of overcompensation, i.e. with minimal pressure assist beyond mere tube compensation. CONCLUSION: In tracheally intubated or tracheostomized spontaneously breathing patients, adequate compensation of tube resistance (i.e. with minimal overcompensation and minimal undercompensation) is best done by the ATC mode.

Aged↗
PubMed2000

Cerebral oxygenation and systemic trauma related factors determining neurological outcome after brain injury.

We examined the relationship between clinical and radiological findings, cerebral oxygenation patterns during intensive care management, presence of systemic trauma related injuries and severity of illness in 50 patients (age: 32.3 +/- 12 years, GCS: 8 +/- 4) who were rescued from the accident scene within a 30 min period after trauma. Presence of systemic injuries was quantified using the Injury Severity Score (ISS) and severity of illness was scored using the Acute Physiology and Chronic Health Evaluation (APACHE II). Cerebral oxygenation parameters included continuous monitoring of jugular bulb oxygen saturation (SjvO(2)) for 12 840 h, and 2323 periodical blood sampling for measurement of arteriovenous differences in oxygen content (AVDO(2)), arteriovenous difference of lactate (AVDL) and lactate oxygen index (LOI). Fifteen patients (30%) presented with anisocoria or non-reacting pupils. Diffuse lesions on computed tomography (CT) were found in 34% of the patients and in 66% a mass lesion was removed. The mean ISS was 28 +/- 15.3 and 34 patients (68%) had an APACHE II score between 20 and 29 (mean 24 +/- 15). No statistically significant association between age (P = 0.45), gender (P = 0.83), initial Glasgow Coma Score (GCS) (P = 0.43), episodes of cerebral perfusion pressure (CPP) < 70 mm Hg (P = 0.8), ISS (P = 0.28), pupillary abnormalities (P = 0.57), initial CT findings (P = 0.74), APACHE II scores (P = 0. 36) and outcome could be demonstrated. The number of SjvO(2)desaturations (< 60%) was the only statistically significant factor associated with outcome (P = 0.05). The percentage of patients with poor neurological outcomes (GOS 1-3) was 38% in patients with no or one desaturation episode, and 57.6% in those with multiple desaturations. In conclusion, in patients who are resuscitated early and quickly transferred to the hospital, the number of SjvO(2)desaturations during intensive care management might be associated with outcome more strongly than other clinical and radiological features.

APACHE↗
PubMed2000

Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients.

OBJECTIVE: To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications. DESIGN: Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions. SETTING: Level I trauma center with emergency room, intensive care unit, and research laboratory. PATIENTS: Four hundred five injured patients with an Injury Severity Score of > or =9 points were enrolled in this study from January 1994 to February 1996. INTERVENTIONS: Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter. MEASUREMENTS AND MAIN RESULTS: We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients' charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9+/-2.5 ng/mL; day 1) or severe MODS (5.7+/-2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1+/-0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS. CONCLUSIONS: These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

APACHE↗
PubMed2000

Incidence and clinical pattern of the abdominal compartment syndrome after "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic trauma.

OBJECTIVE: To investigate the incidence, main physiologic effects, and therapeutic management of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma. DESIGN: Retrospective analysis from January 1991 to December 1996; prospective study from January 1997 to August 1998. SETTING: Level I trauma center, intensive care unit. PATIENTS: A total of 311 patients with severe abdominal and/or pelvic trauma and "damage-control" laparotomy on day of admission. INTERVENTIONS: The ACS was defined as the development of significant respiratory compromise, including elevated inspiratory pressure of >35 mbar, a decreased Horowitz quotient (<150 torr [<20 kPa]), renal dysfunction (urine output, <30 mL/hr), hemodynamic instability necessitating catecholamines, and a rigid or tense abdomen. Beginning with January 1997, urinary bladder pressure as an additional variable for the diagnosis of ACS was continuously measured in patients (n = 12) at risk. Bladder pressures of >25 mm Hg indicated ACS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients (5.5%) developed ACS because of persistent intra-abdominal/retroperitoneal bleeding (n = 12; 70.6%) or visceral edema (n = 5; 29.4%). All patients with ACS underwent primary fascial closure. In eight of these patients (47%), abdominal and/or pelvic packing for hemostasis was performed. All patients with ACS required decompressive emergency laparotomies because of physiologic derangements. The time between primary laparotomy and decompressive laparotomy was 12.9 +/- 2.0 hrs. Emergency decompression of the abdomen resulted in a significant increase in the cardiac index (+146%), tidal volume (+133%), Horowitz quotient (+156%), and urine output (+1557%), whereas bladder pressure (-63%), heart rate (-19%), central venous pressure (-30%), pulmonary artery occlusion pressure (-43%), peak airway pressure (-31%), partial pressure arterial carbon dioxide (-30%), and lactate (-40%) markedly (p < .05) decreased. In two multiply injured patients with additional head trauma, ACS caused a critical increase of the intracranial pressure, which markedly dropped after the release of abdominal tension. CONCLUSIONS: Risk factors for the occurrence of ACS are severe abdominal and/or pelvic trauma, which require laparotomy and packing for the control of hemorrhage. The ACS occurs within hours and causes life-threatening physiologic derangements and a critical rise in intracranial pressure in patients with combined abdominal/pelvic and head trauma. Decompressive laparotomy immediately restores impaired organ functions. In patients at risk, the continuous measurement of urinary bladder pressure as a simple, noninvasive, and less expensive diagnostic tool for early detection of elevated intra-abdominal pressure is mandatory.

Abdomen↗
PubMed2000

Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient mice

-The lipid-lowering antioxidant probucol can inhibit atherosclerosis in animals and restenosis in humans. However, probucol has been shown to promote atherosclerosis in the aortic root of apolipoprotein E-deficient (apoE-/-) mice. In the current study, we examined the effects of probucol on both lesion formation at 4 sites along the aorta and lipoprotein oxidation in the plasma and aortas of apoE-/- mice receiving a diet containing 21.2% (wt/wt) fat and 0. 15% (wt/wt) cholesterol without or with 1% (wt/wt) probucol. After 6 months, controls had developed lesions at all sites investigated. Lesion development was strongly (P=0.0001) affected by probucol, but this effect was not uniform: lesion size was increased in the aortic root but significantly decreased in the arch, the descending thoracic aorta, and proximal abdominal aorta. Plasma and aortas of probucol-treated mice contained high concentrations of probucol and its metabolites (bisphenol and diphenoquinone); increased vitamin C; markedly decreased very low density lipoprotein (but not low density lipoprotein and high density lipoprotein); and decreased cholesterol, cholesteryl esters, triglycerides, vitamin E, and oxidized lipids compared with controls. Interestingly, probucol treatment did not decrease the proportion of aortic lipids that were oxidized. Plasma vitamin C and bisphenol, but not probucol, protected plasma lipids from ex vivo oxidation by peroxyl radicals. These results show that as in other species, probucol can inhibit lesion formation in most parts of the aorta of apoE-/- mice. This effect may involve lipid oxidation-independent mechanisms localized within the vessel wall as well as lipid lowering.

Journal Article↗