Brain-heart crosstalk: the many faces of stress-related cardiomyopathy syndromes in anaesthesia and intensive care.

Neurogenic stress cardiomyopathy (NSC) is a well-known syndrome complicating the early phase after an acute brain injury, potentially affecting outcomes. This article is a review of recent data on the putative role of localization and lateralization of brain lesions in NSC, cardiac innervation abnormalities, and new polymorphisms and other genetic causes of the sympathetic nervous system over-activity. Concerns regarding the management of stress-related cardiomyopathy syndromes during the perioperative period are also discussed. Future clinical research should explore whether specific factors explain different patient susceptibilities to the disease and should be directed towards early identification and stratification of patients at risk, so that such patients can be more carefully monitored and appropriately managed in critical care and during the perioperative period.

[Validity of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) as biomarker of exposure to very low concentrations of carbon disulphide: preliminary results]. / Validiti dell'acido 2-tiotiazolidin-4-carbossilico (TTCA) urinario quale indicatore biologico dell'esposizione a concentrazioni molto basse di solfuro di carbonio: risultati preliminori.

The possibility to use urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) as biomarker of occupational exposure to very low doses of carbon disulphide (CS2) was evaluated preliminarily in 10 workers employed in a chemical plant where rubber vulcanization accelerators are produced, and in 10 workers, residents in the same geographical area and not occupationally exposed to CS2 and dithiocarbamates (DTC). Exposure to airborne CS2 was assessed, only for exposed workers, by both personal and area samplers. For the determination of TTCA, a spot urine sample was collected for each worker, exposed and non exposed, at the end of work-shift. A questionnaire probing lifestyle and dietary habits and non occupational exposure to CS2 and DTC was administered to all workers involved in the study. Environmental exposure to CS2 in 2007 ranged between 0.21 mg/m3 and 0.73 mg/m3 for personal sampling, and between 0.23 mg/m3 and 0.41 mg/m3 for area sampling. Urinary TTCA levels resulted very low and did not show any significant difference between exposed (Median: 10.8 microg/g creat; Range: 6.1-26.4 microg/g creat) and non exposed workers (Median: 9.3 microg/g creat; Range: 3.0-33.0 microg/g creat), while higher, but not significant concentrations of TTCA were observed in smokers than in non smokers (p = 0.09). No correlation was found between urinary TTCA levels and environmental exposure to CS2, age, body mass index, smoking and dietary habits. In conclusion, the low sensibility and specificity in the assessment of occupational exposure to low doses of CS2 in workers compared to general population subjects, makes urinary TTCA a biomarker with a low usefulness in biological monitoring. ACGIH, besides, should also introduce "B" (background) notation, at present not considered for the BEI indicated for urinary TTCA.

Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study.

PURPOSE: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l(-1)), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms(-1)), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg(-1) min(-1), p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

Uracil salvage pathway in PC12 cells.

The salvage anabolism of uracil to pyrimidine ribonucleosides and ribonucleotides was investigated in PC12 cells. Pyrimidine base phosphoribosyl transferase is absent in PC12 cells. As a consequence any uracil or cytosine salvage must be a 5-phosphoribosyl 1-pyrophosphate-independent process. When PC12 cell extracts were incubated with ribose 1-phosphate, ATP and uracil they can readily catalyze the synthesis of uracil nucleotides, through a salvage pathway in which the ribose moiety of ribose 1-phosphate is transferred to uracil via uridine phosphorylase (acting anabolically), with subsequent uridine phosphorylation. This pathway is similar to that previously described by us in rat liver and brain extracts (Cappiello et al., Biochim. Biophys. Acta 1425 (1998) 273; Mascia et al., Biochim. Biophys. Acta 1472 (1999) 93). We show using intact PC12 cells that they can readily take up uracil from the external medium. The analysis of intracellular metabolites reveals that uracil taken up is salvaged into uracil nucleotides, with uridine as an intermediate. We propose that the ribose 1-phosphate-dependent uracil salvage shown by our in vitro studies, using tissues or cellular extracts, might also be operative in intact cells. Our results must be taken into consideration for the comprehension of novel chemotherapeutics' influence on pyrimidine neuronal metabolism.

In vitro recycling of alpha-D-ribose 1-phosphate for the salvage of purine bases.

In this paper, we extend our previous observation on the mobilization of the ribose moiety from a purine nucleoside to a pyrimidine base, with subsequent pyrimidine nucleotides formation (Cappiello et al., Biochim. Biophys. Acta 1425 (1998) 273-281). The data show that, at least in vitro, also the reverse process is possible. In rat brain extracts, the activated ribose, stemming from uridine as ribose 1-phosphate, can be used to salvage adenine and hypoxanthine to their respective nucleotides. Since the salvage of purine bases is a 5-phosphoribosyl 1-pyrophosphate-dependent process, catalyzed by adenine phosphoribosyltransferase and hypoxanthine guanine phosphoribosyltransferase, our results imply that Rib-1P must be transformed into 5-phosphoribosyl 1-pyrophosphate, via the successive action of phosphopentomutase and 5-phosphoribosyl 1-pyrophosphate synthetase; and,in fact, no adenosine could be found as an intermediate when rat brain extracts were incubated with adenine, Rib-1P and ATP, showing that adenine salvage does not imply adenine ribosylation, followed by adenosine phosphorylation. Taken together with our previous results on the Rib-1P-dependent salvage of pyrimidine nucleotides, our results give a clear picture of the in vitro Rib-1P recycling, for both purine and pyrimidine salvage.

In vitro assessment of salvage pathways for pyrimidine bases in rat liver and brain.

In this paper we extend our previous observation on the mobilization of the ribose moiety from guanosine to xanthine catalyzed by rat liver extracts (Giorgelli et al., Biochim. Biophys. Acta 1335 (1997) 16-22). The data show that in rat liver and brain extracts the activated ribose, stemming from inosine and guanosine phosphorolysis as ribose 1-phosphate, can be used to salvage uracil to uracil nucleotides. Uridine is an intermediate. The salvage process occurs even in the presence of excess inorganic phosphate suggesting that uridine phosphorylase may function in vivo as an anabolic enzyme. Ribose 5-phosphate cannot substitute for inosine, guanosine or ribose 1-phosphate as ribose donor. When inorganic phosphate was substituted with arsenate, hindering the formation of ribose 1-phosphate, no ribose transfer could be observed. A similar pathway occurs at the deoxy level. The deoxyribose moiety of deoxyinosine can be used to salvage thymine to thymine nucleotides, again in the presence of excess inorganic phosphate. Our results introduce a novel aspect of the salvage pathway, in which ribose 1-phosphate seems to play a pivotal role.

Ribose 1-phosphate and inosine activate uracil salvage in rat brain.

The purpose of this study was to determine the mechanism by which inosine activates pyrimidine salvage in CNS. The levels of cerebral inosine, hypoxanthine, uridine, uracil, ribose 1-phosphate and inorganic phosphate were determined, to evaluate the Gibbs free energy changes (deltaG) of the reactions catalyzed by purine nucleoside phosphorylase and uridine phosphorylase, respectively. A deltaG value of 0.59 kcal/mol for the combined reaction inosine+uracil <==> uridine+hypoxanthine was obtained, suggesting that at least in anoxic brain the system may readily respond to metabolite fluctuations. If purine nucleoside phosphorolysis and uridine phosphorolysis are coupled to uridine phosphorylation, catalyzed by uridine kinase, whose activity is relatively high in brain, the three enzyme activities will constitute a pyrimidine salvage pathway in which ribose 1-phosphate plays a pivotal role. CTP, presumably the last product of the pathway, and, to a lesser extent, UTP, exert inhibition on rat brain uridine nucleotides salvage synthesis, most likely at the level of the kinase reaction. On the contrary ATP and GTP are specific phosphate donors.

Recycling of alpha-D-ribose 1-phosphate for nucleoside interconversion.

Mobilization of the ribose moiety and of the amino group of guanosine may be realized in rat liver extract by the concerted action of purine nucleoside phosphorylase and guanase. Ribose 1-phosphate formed from guanosine through the action of purine nucleoside phosphorylase acts as ribose donor in the synthesis of xanthosine catalyzed by the same enzyme. The presence of guanase, which irreversibly converts guanine to xanthine, affects the overall process of guanosine transformation. As a result of this purine pathway, guanosine is converted into xanthosine, thus overcoming the lack of guanosine deaminase in mammals. Furthermore, in rat liver extract the activated ribose moiety stemming from the catabolism of purine nucleosides can be transferred to uracil and, in the presence of ATP, used for the synthesis of pyrimidine nucleotides; therefore, purine nucleosides can act as ribose donors for the salvage of pyrimidine bases.

A cross-sectional nationwide survey on esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Our study aims at disclosing epidemiology and most relevant clinical features of esophageal atresia (EA) pointing to a model of multicentre collaboration. METHODS: A detailed questionnaire was sent to all Italian Units of pediatric surgery in order to collect data of patients born with EA between January and December 2012. The results were crosschecked by matching date and place of birth of the patients with those of diagnosis-related group provided by the Italian Ministry of Health (MOH). RESULTS: A total of 146 questionnaires were returned plus a further 32 patients reported in the MOH database. Basing on a total of 178 patients with EA born in Italy in 2012, the incidence of EA was calculated in 3.33 per 10,000 live births. Antenatal diagnosis was suspected in 29.5% patients. 55.5% showed associated anomalies. The most common type of EA was Gross type C (89%). Postoperative complications occurred in 37% of type C EA and 100% of type A EA. A 9.5% mortality rate was reported. CONCLUSIONS: This is the first Italian cross-sectional nationwide survey on EA. We can now develop shared guidelines and provide more reliable prognostic expectations for our patients.

Temporal relationship between endothelin-1 concentrations and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Endothelin 1 (ET-1) is a potent vasoconstrictor that may play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). However, data regarding its pathogenic role in the development of vasospasm are controversial. We planned a prospective, observational clinical study to investigate the temporal relationship between increased ET-1 production and cerebral vasospasm or other neurological sequelae after SAH. METHODS: ET-1 levels in cerebrospinal fluid (CSF) were measured in 20 SAH patients from admission (within 24 hours from the bleeding) until day 7. Patients received a daily transcranial Doppler study and a neurological evaluation. On day 7, angiography was performed to verify the degree and extent of vasospasm. Patients were then classified as having (1) clinical vasospasm, (2) angiographic vasospasm, (3) no vasospasm, or (4) poor neurological condition without significant vasospasm (low Glasgow Coma Scale score [GCS]). RESULTS: On admission, ET-1 levels were increased in the low-GCS group compared with the other groups (P=0.04). On day 4 ET-1 levels were not significantly different among groups, whereas on day 7 ET-1 levels were significantly increased in both the clinical vasospasm and low-GCS groups compared with the angiographic vasospasm and no vasospasm groups (P<0.005). Moreover, when the low-GCS group was excluded, there was a significant relationship between vasospasm grade and CSF ET-1 levels (R(2)=0.73). CONCLUSIONS: CSF ET-1 levels were markedly elevated in patients with clinical manifestations of vasospasm (day 7) and with a poor neurological condition not related to vasospasm. However, ET-1 levels were low in clinical vasospasm patients before clinical symptoms were evident (day 4) and remained low in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe neuronal damage regardless whether this was due to vasospasm or to the primary hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurological deterioration but were not predictive of vasospasm.

Activation pathways of 5-fluorouracil in rat organs and in PC12 cells.

Activation of the pyrimidine analogue 5-fluorouracil (5-FU) to the ribonucleotide level may occur through one of the following three pathways: 1) the 5-phosphoribosyl 1-pyrophosphate (PRPP)-mediated direct transfer of ribose 5-phosphate to 5-FU as catalysed by orotate phosphoribosyltransferase; 2) the ribose 1-phosphate (Rib1-P)-mediated addition of ribose by uridine phosphorylase, followed by the action of uridine kinase; and 3) the 2'-deoxyribose 1-phosphate (deoxyRib1-P)-mediated addition of deoxyribose, thought to be catalysed by thymidine phosphorylase, followed by the action of thymidine kinase. Many of the conclusions as to the precise pathways by which normal tissues and different cell lines activate uracil are indirectly derived from drug interactions affecting the availability of the substrates of the three pathways, or from measurement of activities of the enzymes metabolising 5-FU in normal tissues and tumours. In previous papers (Cappiello et al. Biochim Biophys Acta 1998;1425:273--81; Mascia et al. Biochim Biophys Acta 1999;1472:93--8), we assessed the molecular mechanisms by which the natural base uracil is salvaged in vitro to uracil ribonucleotides and deoxyribonucleotides in rat liver and brain. In this paper, we investigated the pathways of 5-FU activation to cytotoxic ribonucleotide and deoxyribonucleotide levels in normal rat tissues and PC12 cell extracts. The results clearly showed that normal rat tissues activated 5-FU mainly via the Rib1-P pathway, and to a lesser extent via the PRPP pathway. The deoxyRib1-P pathway was absent. PC12 cells activated 5-FU mainly via the PRPP pathway and to a lesser extent by the other two pathways.

Inspiratory effort and measurement of dynamic intrinsic PEEP in COPD patients: effects of ventilator triggering systems.

OBJECTIVE: To investigate effects of ventilator triggering systems (pressure and flow triggering: PT and FT) on measurement of dynamic intrinsic PEEP (PEEPidyn) and patient-ventilator interaction in patients with chronic obstructive pulmonary disease during weaning from mechanical ventilation. DESIGN: Prospective study. SETTING: Medical/surgical intensive care unit of an academic hospital. PATIENTS AND PARTICIPANTS: 6 COPD patients with acute respiratory failure ready to wean. MEASUREMENTS: We measured flow, airway opening, esophageal and gastric pressures. Minute ventilation, breathing pattern and pressure time product (PTP) of the respiratory muscles and of the diaphragm were obtained during spontaneous ventilation through a mechanical ventilator (Puritan-Bennett 7200ae). Two triggering systems, namely PT and FT, were evaluated. RESULTS: The inspiratory muscles effort necessary to overcome the triggering system overestimated PEEPidyn measurement of an amount equal to 49 +/- 2 and 58 +/- 3% during respectively pressure and flow triggering. FT increased tidal volume and minute ventilation and decrease PTP/b and PTP/min of the respiratory muscles and diaphragm. CONCLUSIONS: To correctly measure PEEPidyn, the inspiratory effort produced to overcome PEEPi and to trigger the ventilator must be discriminated. Application of flow triggering requires less effort to initiate inspiration and provide a positive end-expiratory pressure level that is able to unload the respiratory muscles by reducing PEEPi. With flow triggering higher minute ventilation are obtained in COPD patients during the weaning phase.

The accuracy of transcranial Doppler to detect vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: To examine the accuracy of transcranial Doppler to detect cerebral vasospasm in a patient population with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective blind comparison of transcranial Doppler with cerebral angiography. Diagnostic accuracy of transcranial Doppler was assessed using receiver operating characteristic (ROC) analysis and likelihood ratios. Sensitivity and specificity were calculated using directly measured middle cerebral artery diameter as reference standard. SETTING: Intensive Care Unit of a large university teaching hospital. PATIENTS AND PARTICIPANTS: Twenty-two patients with subarachnoid hemorrhage were included. Patients underwent angiography on admission and after 8 days to diagnose vasospasm and were defined as having clinical vasospasm, angiographic vasospasm, or no vasospasm. MEASUREMENTS AND RESULTS: Sensitivity and specificity were 1.00 and 0.75 for angiographic vasospasm and both equal to 1.00 for clinical vasospasm diagnosis. A transcranial Doppler mean velocity threshold value of 100 cm/s for angiographic vasospasm and 160 cm/s for clinical vasospasm detection were chosen by ROC analysis. CONCLUSIONS: A Transcranial Doppler mean velocity threshold of 160 cm/s, calculated by the ROC analysis, accurately detects clinical vasospasm. A daily transcranial Doppler examination performed by a trained operator should be routinely used to provide early identification of patients at high risk and to orient therapeutic decisions.

The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats.

OBJECTIVE: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats. DESIGN: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinephrine (0.08 microgram.kg-1.min-1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ETA/B receptor antagonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique. RESULTS: During the control test, norepinephrine infusion increased CPP by 21 +/- 2 (23 +/- 2%) mmHg (mean +/- SEM; p < 0.001) and CBF by 3.6 +/- 3.1 (6 +/- 8%) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 +/- 1 (20 +/- 2%) mmHg (p < 0.001) and CBF by 15.8 +/- 4.1 (46 +/- 13%) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaCO2 levels were stable during the tests (40.2 +/- 1.4 mmHg). CONCLUSIONS: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.

Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management.

OBJECTIVE: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI). DESIGN: Prospective, interventional study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3-8). INTERVENTIONS: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if % CPP/%CVR < or = 2. RESULTS: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % (+/- 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 +/- 3 to 28 +/- 3 ml/ 100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range. CONCLUSIONS: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.

Patient-ventilator interaction during acute hypercapnia: pressure-support vs. proportional-assist ventilation.

The objective of this study was to compare patient-ventilator interaction during pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) in the course of increased ventilatory requirement obtained by adding a dead space in 12 patients on weaning from mechanical ventilation. With PSV, the level of unloading was provided by setting the inspiratory pressure at 20 and 10 cmH2O, whereas with PAV the level of unloading was at 80 and 40% of the elastic and resistive load. Hypercapnia increased (P < 0.001) tidal swing of esophageal pressure and pressure-time product per breath at both levels of PSV and PAV. During PSV, application of dead space increased ventilation (VE) during PSV (67 +/- 4 and 145 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001). This was due to a relevant increase in respiratory rate (48 +/- 4 and 103 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001), whereas the increase in tidal volume (VT) played a small role (13 +/- 1 and 21 +/- 2% during 20 and 10 cmH2O PSV, respectively, P < 0.001). With PAV, the increase in VE consequent to hypercapnia (27 +/- 3 and 64 +/- 4% during 80 and 40% PAV, respectively, P < 0.001) was related to the increase in VT (32 +/- 1 and 66 +/- 2% during 80 and 40% PAV, respectively, P < 0.001), respiratory rate remaining unchanged. The increase in pressure-time product per minute and per liter consequent to acute hypercapnia and the sense of breathlessness were significantly (P < 0.001) higher during PSV than during PAV. Our data show that, after hypercapnic stimulation of the respiratory drive, the capability to increase VE through changes in VT modulated by variations in inspiratory muscle effort is preserved only during PAV; the compensatory strategy used to increase VE during PSV requires greater muscle effort and causes more pronounced patient discomfort than during PAV.

Usefulness of pyridinium crosslinks and CA 15-3 as markers in metastatic bone breast carcinoma.

Numerous tumor markers such as CEA, MCA, CA 15-3 have been assayed in breast cancer patients to detect relapse at a preclinical stage and most of all to monitor the treatment of the advanced disease. Since they are not site-specific, pyridinium crosslink dosage has recently been reported as a specific bone resorption marker in several non neoplastic diseases. The aim of this study was to evaluate the urinary pyridinium crosslink levels in breast cancer with or without osseous involvement, and to correlate it with serial doses of CA 15-3. 285 breast cancer patients (226 free of disease and 59 with bone metastases) were measured for both pyridinoline and CA 15-3. In the metastatic patients the mean values of the two markers were significantly higher than in non evident disease patients (P = < 0.01 and p = < 0.001 respectively). Abnormal values over the normal were found in 22% for pyridinoline and 11% for CA 15-3 in patients free of disease while the normal values observed in patients with bone metastases were 22% for pyridinoline and 39% for CA 15-3. Tandem dosage of CA 15-3, was highly sensitive but site-aspecific, and pyridinoline, which is bone specific, may be useful chiefly in the monitoring of breast cancer treatment, since many physiological conditions such as age, menopausal status and variation over 24 hours, and cost effectiveness will influence the use of pyridinoline during follow-up.

Relationship of neuron specific enolase and protein S-100 concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury.

Neuron specific enolase (NSE) and protein S-100 have previously been described as markers of brain injury. We aimed to discover whether concentrations of either were raised in arterial and jugular venous serum after traumatic brain injury, and whether serum profiles were related to injury severity and neurological outcome. We recruited 22 patients with a traumatic brain injury who were admitted to the intensive care unit. Paired arterial and jugular venous blood samples were taken on admission, and at 24, 48 and 96 hrs after injury. Samples were analysed for NSE and S-100 by RIA. Concentrations of both NSE and S-100 were increased above controls--mean NSE concentration was highest on admission, whilst mean S-100 peaked at 24 hours after injury. There was a small, but significant difference between jugular venous and arterial concentrations of S-100 (p = 0.022). High NSE and S-100 concentrations were significantly related to poor neurological outcome (p = 0.004 and p < 0.001 respectively). Both serum NSE and S-100 may be of some value in helping to predict outcome after a traumatic brain injury.

Leukocyte adhesion molecule profiles and outcome after traumatic brain injury.

Adhesion molecules have an important role in leukocyte migration into tissue after injury. We hypothesised that changes in ICAM-1 and L-selectin expression after traumatic brain injury would result in altered serum concentrations of these molecules, which would be related to injury severity and outcome. We investigated arterial and jugular venous concentrations of ICAM-1 and L-selectin in 22 patients. The Glasgow Coma Score and Injury Severity Score were recorded. Paired arterial and jugular venous blood samples were taken at designated times after brain injury: on admission, at 24 hours, 48 hours and 96 hours. Glasgow Outcome Scores at 6 months were obtained. Mean serum concentrations of ICAM-1 were normal on admission, but became significantly increased by 96 hours (p = 0.018). Mean L-selectin concentrations wre markedly below controls at all time points (p < 0.001). There were no significant differences between jugular venous and arterial concentrations of either ICAM-1 or L-selectin. Serum ICAM-1 was significantly related to neurological outcome (p < 0.001) and to the Glasgow Coma Score (p < 0.001). These changes in adhesion molecules expression may be important in the pathophysiology of secondary injury. The highly significant relationship between serum ICAM-1 and neurological outcome suggests that drugs which antagonize adhesion molecule activity may improve outcome after traumatic brain injury.

Donation after cardiac death: is a "paradigm shift" feasible in Italy?

Donation after cardiac death (DCD) is one of the growing strategies to overcome the problem of organ shortage. Cardiac death is defined as "irreversible cessation of circulatory and respiratory function"; the time interval to define irreversibility of cardiac death, the peculiarity of consent, and the framework of end-of-life decision making are the most compelling ethical issues which have been raised with DCD. National protocols that balance medical, ethical, and social issues are mandatory to guide transplant care professionals. In Italy, the 20 min cardiac arrest demonstrated by continuous electrocardiography recording is the time interval necessary for death diagnosis based on cardiopulmonary criteria. This time negatively affects donation after cardiac death because warm ischemic time (WIT) - the most important predictor of grafts' poor outcome - is prolonged. However, this time seems to be prudential to define the irreversibility of death and to respect the "dead donor rule", as established by the National Committee of Bioethics. National reference protocols regulating DCD practice are therefore a compelling issue.