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Background: There is a high prevalence of asthma and exercise-induced bronchoconstriction (EIB) in elite athletes when the diagnosis is based on symptoms and medication use. Objective measurements are now required by some sporting bodies to support a diagnosis of asthma or EIB to justify use of beta-agonists. Such measurements could include bronchial provocation with methacholine, with eucapnic voluntary hyperpnea (EVH) of dry air (a surrogate for exercise), or both., Objective: The aim of the study was to investigate the relationship between asthma symptoms and responses to methacholine and the EVH challenge in a group of unselected elite summer-sport athletes. The outcome would be to inform practitioners of a suitable objective approach to identifying those with asthma and EIB., Methods: Fifty elite summer-sport athletes with or without asthma were recruited from sporting teams and sports medicine centers throughout Melbourne, Australia. All subjects completed a respiratory questionnaire and, on separate days, underwent a bronchoprovocation challenge test with methacholine and EVH., Results: Forty-two subjects reported one or more respiratory symptoms in the past year, 9 had positive methacholine challenge results (mean PD(20) of 1.69 +/- 2.05 micromol), and 25 had positive EVH challenge results (mean fall in FEV(1) of 25.4% +/- 15%). Although all subjects with positive methacholine challenge results had positive EVH challenge results, methacholine had a negative predictive value of only 61% and a sensitivity of 36% for identifying those responsive to EVH., Conclusion: These findings suggest that the pathogenesis of EIB in elite athletes might be different from that of asthma, and as such, neither symptoms nor the methacholine challenge test should be used exclusively for identifying EIB.

The phagocytic function of neutrophils is a crucial element in host defense against invading microorganisms. Patients with diffuse peritonitis depend on adequate reactivity of neutrophils, in particular locally in the peritoneal cavity as well as in the circulation. This study examined phagocytosis as well as numerical expression of Fcgamma I-III (CD16, CD32, CD64) and complement receptors (CD18, CD35) of emigrated, intra-abdominal and circulating neutrophils during human secondary peritonitis using fluorescence-activated cell analysis. Optimally opsonized E. coli bacteria were used independently of the well-known low level of opsonic molecules during peritonitis. Compared with controls (abdominal surgery without peritonitis), the percentage of emigrated neutrophils which engulfed E. coli bacteria was significantly depressed until 48 h after diagnosis of, and surgery for, peritonitis. When patients with complicated peritonitis (septic shock, multiple organ failure) were compared with patients without complications, phagocytosis was even more depressed in patients with complications. Numerical expression of CD64 (Fcgamma RI) and CD35 (CR1) increased significantly on emigrated polymorphonuclear leukocytes (PMNs) during peritonitis when compared to controls. There was no difference in CD18 and CD32 (Fcgamma RII) expression between the two groups. Numerical expression of CD16 (Fcgamma RIII) on emigrated PMNs decreased significantly in peritonitis. This was more pronounced in patients with complicated peritonitis. We conclude that there is a long-lasting depression of phagocytosis by emigrated PMNs during peritonitis, independent of the opsonic activity. Our data suggest that decreased phagocytosis might be correlated to the profound drop in CD16 on these cells., (Copyright 2002 S. Karger AG, Basel)

Exercise-induced asthma (EIA) is a common, yet often unrecognized condition occurring in both known asthmatics and otherwise healthy individuals. Misdiagnosis, both over- and underdiagnosis, is not uncommon. In order to accurately diagnose EIA, a bronchoprovocation challenge test must be performed; the current recommended test is a eucapnic hyperventilation (EVH) challenge test. Although there are a number of treatment options available, both pharmacologic and nonpharmacologic, in most cases medications are required. A range of medications are currently available to either treat or prevent EIA. It is important that the medications used are individualized to the patients needs and monitored to ensure efficacy.

Objective: Arterial vasodilation with concomitant hyperdynamic circulation are common findings in liver cirrhosis. Nitric oxide acting at a local level has been suggested to be pathophysiologically relevant in this context. Several systemic factors in conjunction with nitric oxide might interfere with the observed phenomena., Design: The study has been designed to demonstrate the influence of cirrhotic serum on the nitric oxide system and vascular contractility., Methods: The contractile response of aortic segments from healthy rats was studied in vitro after incubation with serum of healthy and cirrhosis-induced rats (1 week, 2 weeks, 3 weeks and 4 weeks after bile duct ligation). A cumulative dose response curve to phenylephrine (10--10-4 mol) was established before and after incubation with nitric oxide synthesis blocker N(omega)-nitro-L-arginine, the more selective aminoguanidine (nitric oxide synthase [NOS]-2 inhibitor) and W7 (NOS-3 inhibitor). NOS-2 expression in incubated aortic rings was evaluated by Western blot analysis., Results: A 4-hour incubation with serum of cirrhosis-induced rats reduced the maximum contractile response to phenylephrine to 66.8 +/- 9.1% after 1 week, 50.4 +/- 7.8% after 2 weeks, 43.2 +/- 2.8% after 3 weeks and 35 +/- 5.2% after 4 weeks of bile duct ligation. This reduction in the contractility response to phenylephrine was completely reversed by blocking nitric oxide synthesis with N(omega)-nitro-L-arginine and aminoguanidine, but not after W7. Incubation with cirrhotic serum induced NOS-2 expression in aortic rings. In Western blot analysis, the most intensive signal for NOS-2 protein was obtained in rings incubated with serum from rats 3 weeks and 4 weeks after induction of cirrhosis., Conclusions: Cirrhotic serum decreases the contractile response to phenylephrine even in an early stage of secondary cirrhosis. Reversibility of this effect after nitric oxide synthesis blockade suggests an induction of nitric oxide synthesis by systemic factors as a major point in vascular hyporeactivity to vasoconstrictors in cirrhosis.

The purpose of the study was to characterize oxygen radical generation by emigrated, intraabdominal and circulating polymorphonuclear leukocytes (ePMNLs and cPMNLs) during peritonitis, as well as to assess any differences between oxygen radical production in patients with low Mannheim peritonitis index (MPI < 26, group 1) or high Mannheim peritonitis index (MPI > or = 26, group 2). Lucigenin-enhanced chemiluminescence was used to determine spontaneous and stimulated (FMLP, PMA, and A23 187) oxygen radical generation by ePMNLs and cPMNLs. In group 1 spontaneous and stimulated oxygen radical generation by emigrated PMNLs was markedly enhanced compared to circulating PMNLs (e.g., spontaneous oxygen radical generation: 30.3 +/- 11.8 cpm/cPMNLs versus 107 +/- 46 cpm/ePMNLs, P < 0.05) . In group 2 oxygen radical generation by cPMNLs markedly increased within 48 h after diagnosis of peritonitis and surgery, contrary to radical generation by ePMNLs (e.g., A23 187-stimulated oxygen radical generation 993.7 +/- 350 cpm/cPMNLs versus 285.6 +/- 77 cpm/ePMNLs, P < 0.05. In conclusion, cPMNLs and ePMNLs exhibit marked polymorphism in their capacity to generate oxygen radicals in response to secondary peritonitis. Severe peritonitis (MPI - 26) was associated with a strong increase in oxygen radical generation by cPMNLs without a parallel activity being manifest by ePMNLs.

The SOFA score, a new system for patients with sepsis-related diseases, was introduced in 1994 by the "Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine." The purpose of this study was to compare the new SOFA score with the APACHE II and MOD scores. The data on 874 patients from a surgical intensive care unit in an university hospital were analyzed using commercially available software (SPSS for Windows, Version 7.5.2 and MS Excel '97). To compare the different scores, receiver-operating characteristics (ROC)--analyses were applied. The study demonstrated clear correlation between an elevated SOFA score and the mortality of the patients during their ICU stay (score 0-->mortality 0%, 1-->3.6%, 2-->22.5%, 3-->86.7%, respectively r = 0.445; P = 0.01). The ROC analyses of the APACHE II, the MOD and the SOFA scores were comparable (area under the curve: APACHE II 0.73, MOD 0.77, SOFA 0.71). In conclusion, the SOFA score is reliable and might be useful in the daily routine of an intensive care unit.

Exercise-induced asthma, as recognized in asthmatic subjects, is an exaggerated airway response to airway dehydration in the presence of inflammatory cells and their mediators. The airway narrowing is primarily caused by contraction of bronchial smooth muscle. The milder airway narrowing documented in response to exercise in elite athletes and otherwise healthy subjects may simply be the result of the physiologic responses and pathologic changes in airway cells arising from dehydration injury. These changes, which include excessive mucus production and airway edema, would serve both to cause cough and to amplify the narrowing effects of normal bronchial smooth muscle contraction, resulting in symptoms. These changes are more likely to occur in healthy subjects who exercise intensely for long periods of time breathing cold air, dry air, or both. Under these conditions, the ability to humidify inspired air may be overwhelmed, causing significant dehydration of the airway mucosa and an increase in osmolarity, even in small airways. In addition to dehydration injury, airway narrowing to pharmacologic and physical agents may occur as a result of injury caused by large volumes of air containing irritant gases, particulate matter, or allergens being inspired during exercise. As a result, the airways may become inflamed, and the airway smooth muscle may become more sensitive. These events could result in the same exaggerated airway response to dehydration, as documented in asthmatic subjects.

The purpose of the study was to examine the effects of buflomedil hydrochloride (BFL) on the expression of adhesion molecules (beta2-integrins) and oxygen radical production of circulating and emigrated intra-abdominal polymorphonuclear leukocytes (PMNL) in a standardized porcine model of hyperdynamic endotoxemia. A total of 20 anesthetized pigs were randomly assigned to one of the following groups: endotoxin group (endotoxin 5 microg / kg x h, intravenously (i.v.), n = 7), BFL group (BFL (3 mg/kg initial i.v. bolus followed by a continuous infusion (.1 mg / kg x h) and endotoxin 5 microg / kg x h, i.v., n = 7), and control group (NaCl .9%; n = 6). Experiments were terminated at 330 min. Infusion of endotoxin alone resulted in the activation of circulating and emigrated PMNL as evidenced by neutropenia, functional and numerical up-regulation of beta2-integrins, and enhanced oxygen radical production. BFL was able to attenuate functional and numerical up-regulation of beta2-integrins as well as oxygen radical production of circulating and emigrated PMNL. An unexpected decrease in the plasma concentration of BFL during the experiments was associated with an increase in the oxygen radical production of PMNL at the end of the experiments. In addition, BFL attenuated the fall in the intramucosal pH and the increase in plasma concentration of lactate observed in the late phase of endotoxemia. These findings suggest that BFL is able to decrease systemic activation of PMNL and to improve local tissue oxygenation during endotoxemia.

Objectives: To determine the effects of a prophylactic intravenous infusion of adenosine on cardiopulmonary functions and oxygen-derived variables in a porcine model of endotoxemia., Design: Prospective, randomized, placebo-controlled, unblinded study., Setting: University research laboratory., Subjects: Thirty country bred pigs, aged 6 to 7 wks, weighing 24.9 +/- 0.65 (SEM) kg body weight., Interventions: Pigs were anesthetized by i.v. pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/oxygen = 1:1. Intravascular catheters were inserted to allow for determination of arterial, central venous blood pressure, pulmonary artery occlusion pressure, cardiac output, and sampling of blood for gas analyses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmonella abortus equi endotoxin (5 microg/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 microg/kg body weight x min), started 30 mins before the infusion of endotoxin. Control groups 3 and 4 (n = 5 for both groups) received adenosine or physiologic saline, respectively., Measurements and Main Results: Parameters of cardiopulmonary function and oxygen-derived variables were calculated from pulmonary artery catheter measurements and blood gas analyses using standard formula. Plasma concentrations of purine compounds (adenosine, inosine, hypoxanthine) were determined by high-performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrations of this cytokine were determined in serum by enzyme-linked immunosorbent assay. Infusion of adenosine before the beginning of the infusion of endotoxin increased plasma concentrations of the nucleoside from 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under control conditions, adenosine did not aggravate the arterial hypotension elicited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular performance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery almost doubled. This adenosine-induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the attenuation of the decrease in the gastric mucosal pHi. No effects of adenosine were observed on the endotoxin-induced increase in serum concentrations of tumor necrosis factor-alpha., Conclusions: Infusion of adenosine might be useful to improve flow-dependent oxygen delivery and tissue oxygenation during endotoxic shock without the induction of adverse cardiopulmonary side effects. The beneficial hemodynamic effects of adenosine appear not to be mediated by the inhibition of the release of tumor necrosis factor-alpha.

The protein apocrustacyanin C1 has been crystallized by vapour diffusion in both microgravity (the NASA space shuttle USML-2 mission) and on the ground. Rocking width measurements were made on the crystals at the ESRF Swiss-Norwegian beamline using a high-resolution psi-circle diffractometer from the University of Karlsruhe. Crystal perfection was then evaluated, from comparison of the reflection rocking curves from a total of five crystals (three grown in microgravity and two earth controls), and by plotting mosaicity versus reflection signal/noise. Comparison was then made with previous measurements of almost 'perfect' lysozyme crystals grown aboard IML-2 and Spacehab-1 and reported by Snell et al. [Snell, Weisgerber, Helliwell, Weckert, Holzer & Schroer (1995). Acta Cryst. D51, 1099-1102]. Overall, the best diffraction-quality apocrustacyanin C1 crystal was microgravity grown, but one earth-grown crystal was as good as one of the other microgravity-grown crystals. The remaining two crystals (one from microgravity and one from earth) were poorer than the other three and of fairly equal quality. Crystal movement during growth in microgravity, resulting from the use of vapour-diffusion geometry, may be the cause of not realising the 'theoretical' limit of perfect protein crystal quality.

The end-systolic pressure-volume relation (ESPVR) is accepted as a load-independent measure of cardiac contractility. Potential curvilinearity of the ESPVR, dependency on coronary perfusion pressure (CPP) and sensitivity to the type of loading intervention might limit its use in hemorrhagic shock. This study compared ESPVRs obtained by caval and aortic occlusion under physiological loading conditions at baseline with those obtained during hemorrhagic shock (mean arterial pressure 45 mmHg). The left ventricular (LV) pressure (tip manometer) and volume (conductance catheter) were measured in ten anesthetized pigs. ESPVRs were fitted to linear and quadratic models. Within end-systolic pressure (Pes) ranges obtained under baseline conditions, ESPVR displayed only minimal curvilinearity (second-order coefficient a < 0.007) and could be accurately described by a linear model. However, nonlinearity of ESPVRs obtained over wider load ranges is suggested by negative volume axis intercepts of the linear model. Steeper ESPVR with aortic than with caval occlusion (2.28 +/- 0.22 vs 3.41 +/- 0.51 mmHg/ml, ns) could not be proven owing to the large interindividual variance of ESPVR slopes with both loading interventions. During shock the Pes range obtained by caval occlusion decreased to very low levels (from 49 +/- 2 to 34 +/- 1 mmHg), ESPVR did not adequately fit either of the two models (mean R < 0.66), and critical reduction of CPP induced negative ESPVR slope in four of ten experiments. In contrast, aortic occlusion at shock resulted in linear ESPVR (R = 0.927 +/- 0.029), Pes ranges (92 +/- 3 to 58 +/- 4 mmHg) comparable to the ones obtained by caval occlusion at control (113 +/- 5 to 73 +/- 6 mmHg), and steeper ESPVR than at control (3.41 +/- 0.51 to 7.38 +/- 1.0 mmHg/ml, P < 0.05). Interpretation of the increased ESPVR slope obtained with aortic occlusion as due to increased contractility in shock is, however, complicated by different Pes ranges. It is concluded that within Pes ranges obtained with caval or aortic occlusion in situ the ESPVR can be adequately fitted to a linear model. For assessment of the inotropic response to shock the ESPVR is of limited value because (1) caval occlusion is not suitable to generate ESPVR during shock, and (2) Pes ranges obtained with identical loading interventions differ greatly between baseline and shock and, therefore, apparent ESPVR changes are influenced by the potential nonlinearity of the ESPVR. Combining caval occlusion at baseline with aortic occlusion at shock would result in comparable Pes ranges. Interpretation of results is, however, complicated by diverging effects of the different loading interventions on the shape and slope of the ESPVR.

From our own experience with 104 patients with liver trauma treated by laparotomy we confirmed the present trends in treating blunt liver trauma, i.e. conservative therapy of minor lesions under closed observation with imaging procedures (US and CT-scan); minor local measures in superficial liver injuries when laparotomy is performed for other reasons; generous use of the Pringle maneuver in primary hemostasis; temporary or final treatment by perihepatic packing in all parenchymal fractures with predominant venous bleeding; direct suture or ligation of arterial bleeding; liver resection only for the debridement of destroyed tissue. With primary packing the patient can be transferred to an experienced center. The overall mortality is more dependent on combined lesions from polytrauma. The early and efficient hemostasis of liver trauma may, however, stabilize the border-line patient and give him a better chance. This is underlined by the experience, that isolated liver injuries have a much better prognosis except central lesions of the retrohepatic vena cava and large central hepatic veins.

Between 1972 and 1988, a total of 57 patients with an average birth weight of 1988 g and an average gestational age of 34.1 weeks were operated on for neonatal necrotizing enterocolitis. In 48% of the cases, the critical indication for surgery was determined by clinical examination; in 52% of the cases, the indication was based upon a radiological diagnosis of pneumoperitoneum. The affected intestinal portions were first resected. Then, the proximal and distal limbs were sewn together and brought out through a separate short incision. Utilizing this procedure, the lethal rate sank from above 80% to below 30%. Taking into account unrelated causes of death, no significant increase in risk has been associated with the use of this procedure on prematurely born patients and patients exhibiting acute intestinal perforations.

We determined the water-soluble thiol (SH) content and the osmolality of the cell sap in spruce trees of both low- and high-altitude origin that were transplanted to two test areas at different altitudes (400 m and 1700 m). There was little or no significant difference in SH content and osmotic value between trees of low- or high-altitude origin at the same altitude, but the sulfhydryl (SH) content varied with the altitude of cultivation, being higher at 1700 m than at 400 m. SH content and osmotic value were higher in winter, independent of altitude and provenance. The annual pattern of water-soluble and protein-bound SH content and glutathione reductase activity was measured in spruce trees at 1700 m; these values also peaked in winter and were lowest in summer.

From 1985 to 1988, six patients suffered from short gut syndrome due to congenital malformations. The children were aged 4-24 months at the time of the operation in which the gut was doubled in length by a Bianchi procedure. It is necessary to interview the parents about their own and the child's psychological and physical stress during the pre- and postoperative periods. Collective reactions were found which must be considered for indication and time of operation.