Deadly diving? Physiological and behavioural management of decompression stress in diving mammals.

Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N(2)) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N(2) tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N(2) loading to management of the N(2) load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.

Development of a risk stratification model for predicting acute renal failure in orthotopic liver transplantation recipients.

The purpose of this prospective observation cohort study was to develop and validate a risk stratification model for prediction of acute renal failure after liver transplantation. Data from 71 orthotopic liver transplantation recipients were used to develop a risk stratification model by binary logistic regression analysis containing the following variables: pretransplant hepatitis B and/or C infection; arterial hypertension; intra-operative mean arterial blood pressure before induction of anaesthesia; units of packed red blood cells required; hypotension (mean arterial blood pressure

Breathing pattern, CO2 elimination and the absence of exhaled NO in freely diving Weddell seals.

UNLABELLED: Weddell seals undergo lung collapse during dives below 50 m depth. In order to explore the physiological mechanisms contributing to restoring lung volume and gas exchange after surfacing, we studied ventilatory parameters in three Weddell seals between dives from an isolated ice hole on McMurdo Sound, Antarctica. METHODS: Lung volumes and CO(2) elimination were investigated using a pneumotachograph, infrared gas analysis, and nitrogen washout. Thoracic circumference was determined with a strain gauge. Exhaled nitric oxide was measured using chemiluminescence. RESULTS: Breathing of Weddell seals was characterized by an apneustic pattern with end-inspiratory pauses with functional residual capacity at the end of inspiration. Respiratory flow rate and tidal volume peaked within the first 3 min after surfacing. Lung volume reductions before and increases after diving were approximately 20% of the lung volume at rest. Thoracic circumference changed by less than 2% during diving. The excess CO(2) eliminated after dives correlated closely with the duration of the preceding dive. Nitric oxide was not present in the expired gas. CONCLUSION: Our data suggest that most of the changes in lung volume during diving result from compression and decompression of the gas remaining in the respiratory tract. Cranial shifts of the diaphragm and translocation of blood into the thorax rather than a reduction of thoracic circumference appear to compensate for lung collapse. The time to normalise gas exchange after surfacing was mainly determined by the accumulation of CO(2) during the dive. These findings underline the remarkable adaptations of the Weddell seal for restoring lung volume and gas exchange after diving.

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. / Computertomographische Kriterien für den zu erwartenden Effekt von inhaliertem Stickstoffmonoxid bei Patienten mit schwerem akutem Lungenversagen.

PURPOSE: Inhaled nitric oxide (iNO) is an effective therapy for severe hypoxemia in most patients with acute respiratory distress syndrome (ARDS). For unknown reason, a subset of ARDS patients does not respond favorably to iNO therapy. We hypothesized that radiological manifestation of lung injury may be related to iNO response. MATERIALS AND METHODS: We retrospectively analyzed data from n = 25 ARDS patients who received iNO, and underwent chest CT within 72 h prior to inhaled treatment. The morphology of coherently pathologic lung tissue was characterized by the length of the borderline between consolidated, infiltrated and atelectatic lung tissue and radiologically normal lung tissue. This quantity was expressed as relative fraction of the visceral pleural circumference and averaged over all CT slices. Furthermore we semiquantitatively determined the total volume of consolidated lung tissue as part of the whole lung. RESULTS: In n = 6 non-responders to iNO (DeltaPaO2 < 10 %), we determined a short relative borderline between normal and consolidated lung tissue due to the presence of large and coherently consolidated lung regions. In n = 19 iNO responders (DeltaPaO2 > 10 %), we found significantly less coherently consolidated lung tissue evidenced by an increased relative borderline when compared to iNO non-responders (0.09 +/- 0.02 vs. 0.1 +/- 0.01; P < 0.05). Moreover, there was a moderate and significant correlation between DeltaPaO2 induced by iNO and the relative borderline in all patients studied (R = 0.59; P < 0.05). Total fraction of consolidated lung tissue volume was not different between iNO non-responders and responders (60 +/- 3 % vs. 54 +/- 2 % n. s.). CONCLUSION: Our data demonstrate that the gross morphological distribution of pathological lung tissue influences iNO response in ARDS. Inhaled NO was most beneficial in injured lungs characterized by many small consolidated areas surrounded by normal lung tissue. The increased borderline between pathologic and normal lung tissue offers additional possibility for iNO to divert blood flow from shunt areas to ventilated lung regions, which consequently improves arterial oxygenation.

[Preoperative fasting. An update]. / Präoperative Nahrungskarenz. Ein update.

In Germany the predominant standard of preoperative care for elective surgery is fasting after midnight, with the aim of reducing the risk of pulmonary aspiration. However, for the past several years the scientific evidence supporting such a practice has been challenged. Experimental and clinical studies prove a reliable gastric emptying within 2 h suggesting that, particularly for limited intake of clear fluids up to 2 h preoperatively, there would be no increased risk for the patient. In addition, the general incidence of pulmonary aspiration during general anaesthesia (before induction, during surgery and during recovery) is extremely low, has a good prognosis and is more a consequence of insufficient airway protection and/or inadequate anaesthetic depth rather than due to the patient's fasting state. Therefore, primarily to decrease perioperative discomfort for patients, several national anaesthesia societies have changed their guidelines for preoperative fasting. They recommend a more liberal policy regarding per os intake of both liquid and solid food, with consideration of certain conditions and contraindications. The following article reviews the literature and gives an overview of the scientific background on which the national guidelines are based. The intention of this review is to propose recommendations for preoperative fasting regarding clear fluids for Germany as well.

Response of neonatal platelets to nitric oxide in vitro.

OBJECTIVES: Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro. DESIGN: Umbilical cord and venous (mother, controls) platelet-rich plasma was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry. SETTING: Delivery department of an university hospital. PATIENTS AND PARTICIPANTS: Ten healthy term neonates, their mothers and nonpregnant controls. MEASUREMENTS AND RESULTS: NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but the relative response to SIN-1 was similar in all three groups (70 +/- 5 %). CONCLUSIONS: The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.

Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema.

An exaggerated hypoxic pulmonary vasoconstriction is essential for development of high-altitude pulmonary edema (HAPE). We hypothesized that susceptibility to HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decrease in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmonary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susceptible mountaineers and nine HAPE-resistant control subjects during normoxia and acute hypoxia (fraction of inspired oxygen [FI(O2)] = 0.12). The subjects performed oral breathing. Nasally excreted NO was separated from respiratory gas by suction via a nasal mask. In HAPE-susceptible subjects, NO excretion in expired gas significantly decreased (p < 0.05) during hypoxia of 2 h in comparison with normoxia (28 +/- 4 versus 21 +/- 2 nl/min, mean +/- SEM). In contrast, the NO excretion rate of control subjects remained unchanged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not differ significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not influenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in lower respiratory tract NO excretion (R = -0.49, p = 0.04). Our data provide the first evidence of decreased pulmonary NO production in HAPE-susceptible subjects during acute hypoxia that may contribute among other factors to their enhanced hypoxic pulmonary vascular response.

[Intensive care management of ARDS]. / Intensivmedizinisches Management des ARDS.

The acute respiratory distress syndrome (ARDS) is characterized by (1) intrapulmonary right-to-left shunting, (2) permeability edema of the lung, and (3) alterations in pulmonary compliance. The clinical features of ARDS are due to an acute inflammatory reaction of the lung. Current clinical management of patients with ARDS aim at implementation of lung protective ventilatory strategies with adequate PEEP and low tidal volumes, diagnosis and treatment of underlying infections, and a negative fluid balance together with positional maneuvers like prone positioning.

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise.

OBJECTIVE: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers. DESIGN: Prospective observational study. SETTING: University laboratory. PARTICIPANTS: Fourteen healthy adult volunteers. INTERVENTIONS: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min. MEASUREMENT AND RESULTS: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 +/- 89 nl/min for non-smokers and 261 +/- 142 nl/min for smokers (mean +/- SD, n.s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 +/- 21 nl/min versus 23 +/- 14 nl/min, p < 0.05; smokers: 41 +/- 8 nl/min versus 22 +/- 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 +/- 3.1 ppb at rest and this decreased to 9.3 +/- 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 +/- 2 to 21 +/- 3 l/min. CONCLUSION: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.

Dose-dependent effects of almitrine on hemodynamics and gas exchange in an animal model of acute lung injury.

OBJECTIVE: To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN: Prospective, randomized, controlled study. METHODS: Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 micrograms.kg-1.min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 micrograms.kg-1.min-1 improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg for Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Qs/Qt) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm > or = 8.0 micrograms.kg-1.min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 micrograms.kg-1.min-1, high doses > or = 8.0 micrograms.kg1.min-1 decreased PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Qs/Qt (67 +/- 10% for Alm 16.0) (P < 0.05). CONCLUSIONS: In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.

[Postoperative analgesia in children after hernioplasty. Wound infiltration with different concentrations of bupivacaine: a pilot study]. / Postoperative Analgesie bei Kindern nach Hernioplastie. Wundinstillation mit verschiedenen Konzentrationen von Bupivacain: eine Pilotstudie.

UNLABELLED: Wound instillation seems to be an easy and preferable way to achieve postoperative analgesia in pediatric hernioplasty. This prospective, randomized and double-blinded pilot-study was initiated to gain preliminary information in order to define the appropriate concentration of local anaesthetic for efficient posthernioplastic analgesia. METHOD: 29 children aged 3.1 to 13.7 (5.25 (3.8-8.2) years were randomly assigned to receive either 0.2 ml/kg bupivacaine 0.125% (n = 10), bupivacaine 0.25% (n = 10) or bupivacaine 0.5% (n = 9). The local anesthetic (LA) was instillated intraoperatively before wound closure above the external oblique muscle and below Scarpa's fascia. After entering the post-anesthetic care unit (PACU) pain was assessed by a trained nurse using the linear analogue pain scale (LAPS) in intervals of 15 min. Patients were observed in the PACU for 30-60 min. Pain was further evaluated for 5.5(3-6) h in the ward every hour. In day-only patients the parents were contacted 24 h postoperatively to obtain additional information. RESULTS: From the beginning of the observation period the 0.5% group tended to have less pain than the others in the PACU. The 0.125% and 0.25% group required earlier supplementary analgetics. In addition, the 0.5% group needed once (1/9) supplementary analgesics; the 0.25% group five times (5/10) and the 0.125% group six times (6/10). None of these results is statistically significant, though they appear to be clinically relevant. DISCUSSION: Wound instillation with 0.2 ml of bupivacaine 0.5% seems to be easy to perform, safe and efficient in controlling posthernioplastic pain. Because of the small numbers of patients included however, no statistically significant differences were observed between the groups. Neither in the LAPS on arrival and observation at the PACU nor in the need for supplementary analgesics. Despite lacking significance the clinical impression suggests a difference to be validated by larger studies. Our data implies that wound instillation with 0.2 ml/kg bupivacaine 0.5% should be regarded for routine usage.

Exhaled nitric oxide does not provide a marker of vascular endothelial function in healthy humans.

In the lung, nitric oxide synthase (NOS) has been found in both alveolar epithelial and vascular endothelial cells. Nitric oxide (NO) in the exhaled air stemming from the lower respiratory tract has been claimed to represent a marker of the vascular endothelial NO production. Experimental evidence for this concept, however, is lacking. We compared, in eight healthy volunteers, effects on exhaled NO of epithelial NOS inhibition by N (G)-monomethyl-L-arginine (L-NMMA) inhalation (6 mg/kg over 15 min) with those of endothelial NOS inhibition by L-NMMA infusion (25 microgram/kg/min for 30 min). We also measured blood pressure, heart rate, and L-NMMA plasma concentration. The major new findings were that L-NMMA inhalation which did not have any detectable effect on hemodynamics and L-NMMA plasma concentration, decreased the pulmonary exhaled NO by almost 40%. In contrast, L-NMMA infusion that inhibited endothelial NOS, as evidenced by an increase in blood pressure and a decrease in heart rate, had only a barely detectable effect on exhaled NO (-11 +/- 4% from baseline). Pulmonary exhaled NO is mostly of epithelial rather than endothelial origin, and does not provide a marker for vascular endothelial NO production and/or endothelial function in healthy humans.

Childhood asthma: exhaled nitric oxide in relation to clinical symptoms.

Bronchial asthma is associated with increased levels of exhaled nitric oxide which are suppressible by glucocorticosteroid inhalation. Children with bronchial asthma were studied to elucidate the relation between endogenous NO release and recent symptoms of bronchial obstruction. Twenty-five children with atopic asthma and 11 healthy control subjects were enrolled and exhaled NO was studied using chemiluminescence analysis. The subjects breathed purified air (<0.5 parts per billion (ppb) NO) exclusively through their mouths. Orally expired NO was measured during continuous nasal aspiration (1.3 L x min(-1)) to remove nasally produced NO. Nasal NO concentration was determined within the aspirated gas. Orally expired NO concentration was 2.5+/-0.3 ppb (mean +/-SEM) in healthy control subjects, 3.19+/-0.88 ppb (NS) in symptom-free children, and 8.28+/-0.81 ppb (p< or =0.01) in children with bronchial asthma who had had recent symptoms of bronchial obstruction. Similarly, in the subgroup of children treated regularly with inhaled glucocorticosteroids those with recent symptoms had significantly higher orally exhaled NO concentrations than healthy control subjects (9.5+/-1.5 ppb, p<0.05). The nasal NO concentration was 152.8+/-12.7 ppb in healthy control subjects and not significantly different in asthmatic children. In this group of asthmatic children, recent symptoms of bronchial obstruction were linked to significantly higher concentrations of NO in orally exhaled gas and to increased oral NO excretion rates. If substantiated by further studies, measurement of orally exhaled NO during nasal aspiration may become useful to monitor disease control in asthmatic children.

Exhaled nitric oxide in preterm infants.

Nitric oxide (NO) is detectable in the exhaled gas of adults during spontaneous respiration and, according to current knowledge, mainly originates from the paranasal sinuses. We studied total NO excretion rates by chemiluminescence in preterm infants whose paranasal sinuses are known to be only partially pneumatized. NO excretion was 7.15 +/- 1.13 nl/min (mean +/- SD, range 6.33-9.36 nl/min) measured from spontaneously exhaled nasal gas (n = 6) and 0.3 +/- 0.05 nl/min (range 0.26-0.36 nl/min) measured from the lower airways in intubated individuals (n = 3). These values are considerably lower than those reported for older children and adults. Body weight-related amounts of NO excretion, however, seem comparable between infants and adults.

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses.

To investigate whether relevant levels of nasal nitric oxide (NO) are produced in the absence of paranasal sinuses, we studied 17 healthy baboons, mammals without any paranasal sinuses. The animals were anesthetized with ketamine hydrochloride and breathed spontaneously. While the baboons breathed through a face mask (mouths closed) connected to a respirator, NO concentrations in exhaled gas were sampled from the expiratory limb and analyzed by chemiluminescence. While the animals were breathing ambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration in the exhaled gas was 1.00 +/- 0.59 parts/billion, and NO release was 4.28 +/- 2.72 nl/min. A NO concentration of 4.79 +/- 2.08 parts/billion was found in the nasal gas (NO release: 7.18 +/- 3.13 nl/min). An age-dependent increase in nasal NO levels was not observed. Exhaled and nasal NO concentrations in baboons were markedly lower than in mammals with paranasal sinuses, suggesting that paranasal sinuses might be an anatomic requirement for production of relevant nasal NO levels.

Superimposing positive end-expiratory pressure during partial liquid ventilation in experimental lung injury.

This study was undertaken to determine the effects of superimposing incremental levels of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) on gas exchange, respiratory mechanics and morphological changes in experimental acute lung injury (ALI). In a prospective trial, six pigs weighing 30+/-5 kg (mean+/-SD) were tracheotomized, submitted to pressure-controlled mechanical ventilation (pc-CMV) and depleted of surfactant by lung lavage. Animals were then mechanically ventilated with three levels of PEEP: 0.5, 1.0 and 1.5 kPa. PLV was then initiated by intratracheal instillation of 30 mL x kg(-1) perfluorocarbon, followed by pc-CMV with PEEP 0.5, 1.0 and 1.5 kPa. Computed tomography (CT)-based analyses of lung volumes and density were obtained after lung lavage, in PLV and during the combined application of PLV and PEEP. Simultaneously, haemodynamics, gas exchange, dynamic compliance (Cdyn) and dynamic resistance (Rdyn) were determined. Statistical analysis was performed using multivariate analyses of variance for repeated measures (p<0.05). In ALI and before PLV, the application of PEEP significantly reduced cardiac output and intrapulmonary shunt. Arterial oxygen tension (Pa,O2) was increased from 6.9 kPa (52 (42, 54) mmHg) (median, (25th and 75th percentile)) to 8.6 kPa (65 (52, 133) mmHg) (PEEP 1.0 kPa) and 15.6 kPa (117 (90, 195) mmHg) (PEEP 15 kPa) (p<0.05). The lung volume obtained by CT increased, CT density was reduced (p<0.05), Cdyn tended to increase and Rdyn to decrease (nonsignificant). PLV increased arterial carbon dioxide tension and reduced pH (p<0.05). CT lung volume and lung density were increased (p<0.05). Superimposing PEEP on PLV increased Pa,O2 from 9.3 kPa (70 (52,124) mmHg) (PEEP 0.5 kPa) to 12.9 kPa (97 (55, 233) mmHg) (PEEP 1.0 kPa) and 403 kPa (303 (64, 426) mmHg) (PEEP 1.5 kPa) (p<0.05), but had no significant effect on CT lung volume and density. It was concluded that in experimental lung injury, positive end-expiratory pressure provided alveolar recruitment. The combined application of positive end-expiratory pressure and partial liquid ventilation significantly augmented oxygenation and might eventually allow either a reduction in the volumes of perfluorocarbons required, or a reduction in positive end-expiratory pressure necessary to maintain pulmonary gas exchange in acute lung injury.

Morphological changes in chest radiographs of patients with acute respiratory distress syndrome (ARDS).

OBJECTIVE: To determine whether the quality of infiltrations in chest radiographs can accurately predict the histological extent of fibrotic change in patients with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective clinical investigation. SETTING: Intensive care unit (ICU) of a university teaching hospital. PATIENTS AND METHODS: Of 47 patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS over a 5-year period, 23 patients underwent open lung biopsy at thoracotomy for treatment, mostly of pneumothorax. Chest films obtained by portable chest roentgenography preceding the operation were reviewed retrospectively and compared to the histomorphological results of the lung specimen. RESULTS: Chest radiographs displayed mixed alveolar-reticular opacification in 60.2%, alveolar patterns in 22.9% and reticular opacities in 10.5%. In 0.4% there were no infiltrates, 6% could not be evaluated because of insufficient quality. There was no relevant difference between the right and left lungs. Subdividing patients into two groups according to the histological results of either absent or mild (1) or severe (2) lung fibrosis, we found an alveolar haziness in 12.3% in group 1 compared with 28.2% in group 2, while reticular characteristics were identified in 13% and 11%, respectively. CONCLUSIONS: The most common opacity in chest radiographs of patients with severe ARDS treated with ECMO is mixed alveolar-reticular opacification. Severe lung fibrosis is not positively correlated with a reticular radiographic pattern. ECMO does not lead to specific radiological changes in conventional radiograms, contrary to clinical findings that treatment with ECMO might induce pleural or pulmonic haemorrhage, especially in the earlier days when systemic heparinization had to be used instead of the heparin-coated tube-surfacing.

Nitric oxide inhibits tissue factor synthesis, expression and activity in human monocytes by prior formation of peroxynitrite.

OBJECTIVE: Nitric oxide (NO) has antithrombotic properties by regulating platelet function, whereas direct effects on plasmatic coagulation are rarely described. In sepsis and inflammation, when synthesis of NO, oxygen radicals and toxic metabolites is crucial, the expression of tissue factor (TF) on monocytes stimulated by lipopolysaccharides (LPS) induces intravascular coagulation. This study was performed to examine the influence of NO and the NO-dependent metabolite peroxynitrite on LPS-induced TF expression and activity in human monocytes. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human peripheral blood mononuclear cells were isolated from buffy coats by gradient centrifugation. The NO-releasing compounds SIN1 and NOC18 were used under different conditions. TF antigen was assayed by flow cytometry, and its activity by a clotting assay. TF-mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR-ELISA). MEASUREMENTS AND RESULTS: Whereas NOC18, a pure NO donor, had no effect, SIN1, releasing both NO and superoxide (O2-), reduced TF expression and activity in a dose- and time-dependent manner; superoxide dismutase (SOD) reversed the SIN1-mediated effect. Adding the O2(-)-deliberating system hypoxanthin/xanthin oxidase (which had no significant effect per se) to NOC18, or using the NO and O2- reaction product peroxynitrite resulted in a reduction of TF expression. RT-PCR-ELISA indicated upregulation of TF-mRNA by SIN1 with a peak at 500 microM; higher doses had less effect. CONCLUSION: These data demonstrate an influence of NO on LPS-induced TF expression in monocytes by prior formation of peroxynitrite; furthermore, the balance between NO and O2- seems to play a crucial role.

[Withholding medical care as a physical injury--homicide from the viewpoint of the physician]. / Arztliches Unterlassen als Körperverletzung--fahrlässige Tötung aus Sicht des Arztes.

Limitation and termination of intensive care and in particular life support in patients who do not have a chance to recover from their illness has become a widely accepted approach in intensive care medicine. In well defined situations, life support can be withheld or withdrawn without the risk of becoming a criminal case. Frequently, the physician must base his/her decision on the presumed will of the patient which can be difficult to assess. Existing guidelines of the Society of physicians of Germany, which are partly preliminary, are helpful for the decision process of the physicians as well as of the relatives of the patients.