mTOR pathway activation in large vessel vasculitis.

BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown. METHODS: We evaluate mTORC pathway activation in vascular aorta lesions and in T cell homeostasis of patients with LVV. RESULTS: Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway (S6RP phosphorylation). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. mTORC1 activation was found also in Th1 and Th17 cells both systemically and in inflamed vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNγ+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV. CONCLUSIONS: We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.

Influence of peripheral vascular calcification on efficiency of screening tests for peripheral arterial occlusive disease in diabetes--a cross-sectional study.

AIMS: Pulse palpation and ankle brachial index are recommended to screen for peripheral arterial occlusive disease in people with diabetes. However, vascular calcification can be associated with false negative tests (arteriopathy present despite normal screening tests). We therefore studied the impact of peripheral vascular calcification on the performance of these tests. METHODS: This cross-sectional study included 200 people with diabetes at high risk of cardiovascular disease. The main exclusion factor was an estimated glomerular filtration rate < 30 ml/min. Peripheral arterial occlusive disease was diagnosed by colour duplex ultrasonography and peripheral vascular calcification scored by computed tomography scan. We measured sensitivity, specificity, predictive values, accuracy and likelihood ratios of pulse palpation and ankle brachial index, and looked for the impact of calcification on false negative tests (arteriopathy present despite normal screening tests). RESULTS: Ankle brachial index alone had poor sensitivity and negative predictive value and high negative likelihood ratio. Pulse palpation had higher sensitivity and negative predictive value. An abnormal pulse palpation, defined by weak or missing pulses, combined with an abnormal ankle brachial index, had the highest sensitivity and negative predictive value (92.3 and 89.8%, respectively). Vascular calcification score was higher in patients with false negative tests, for both pulse palpation and ankle brachial index (P < 0.0001 for all). Ankle systolic blood pressure was higher in patients with false negative tests for pulse palpation (P = 0.004). CONCLUSIONS: Below-knee vascular calcification gave a high rate of false negative results for ankle brachial index. Refined pulse palpation combined with ankle brachial index remained the best strategy to screen for peripheral arteriopathy.

An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells.

Understanding biology at the single-cell level requires simultaneous measurements of biochemical parameters and behavioral characteristics in individual cells. Here, the output of individual flagellar motors in Escherichia coli was measured as a function of the intracellular concentration of the chemotactic signaling protein. The concentration of this molecule, fused to green fluorescent protein, was monitored with fluorescence correlation spectroscopy. Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis. This experimental approach can be extended to quantitative in vivo studies of other biochemical networks.

DNA: an extensible molecule.

The force-displacement response of a single duplex DNA molecule was measured. The force saturates at a plateau around 70 piconewtons, which ends when the DNA has been stretched about 1.7 times its contour length. This behavior reveals a highly cooperative transition to a state here termed S-DNA. Addition of an intercalator suppresses this transition. Molecular modeling of the process also yields a force plateau and suggests a structure for the extended form. These results may shed light on biological processes involving DNA extension and open the route for mechanical studies on individual molecules in a previously unexplored range.

[Technological advances in cardiac CT]. / Evolutions technologiques en tomodensitométrie cardiaque.

The SFR-SFC presents guidelines dedicated to cardiac and coronary imaging using CT in the area of indications, technological requirement including both hardware and software, patient conditioning, CT protocols and related results concerning radiation dose, image quality and diagnostic value. These guidelines are based either on up-dated medical literature proofs and/or on expert consensus.

[Cardiac sarcoidosis: Diagnosis and therapeutic challenges]. / Sarcoïdose cardiaque : avancées diagnostiques et thérapeutiques.

Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success.

[Evolution of the treatment of chronic post-traumatic aneurysms of the descending thoracic aorta: 30 years experience]. / Evolution du traitement des anévrismes post-traumatiques chroniques de l'aorte thoracique descendante: une expérience personnelle de 30 ans.

The authors present the early and late results of a series of 40 patients treated for chronic post-traumatic aneurysms of the descending thoracic aorta from 1975 to 2005. With the exception of a patient who died of an intra-pleural rupture before surgery, the patients were treated by aortotomy and prosthetic graft (N=17), aortotomy and direct suture (N=17) or endoprosthesis (N=5). The use of distal aortic perfusion in 22 patients enabled 17 direct sutures (77.3%) thanks to extensive mobilisation of the aortic arch. Endoprostheses have been used since 1997 in high surgical risk patients with severe comorbid conditions. There were no deaths, one transient paraparesia after simple aortic clamping, one reoperation for a haemothorax and four cases of dysphonia due to paralysis of the recurrent laryngeal nerve. Thirty-five patients (90%) were followed up for an average of 119.7 +/- 16.4 months. There were no clinical complications and the late morphological results were good in all cases with the exception of one type 1 endoprosthetic leak. The treatment of chronic post-traumatic aneurysms of the descending thoracic aorta gives excellent early and late results, justifying wide operative indications. The wish to avoid use of a prosthesis in young patients with a long life expectancy should give preference to conventional surgical techniques which, providing distal aortic perfusion is employed, allow direct suture of three quarters of cases. Endovascular treatment is reserved only for "poor surgical risks".

Percutaneous transluminal angioplasty in severe diabetic foot ischemia: outcomes and prognostic factors.

OBJECTIVES: To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were sought. RESEARCH DESIGN AND METHODS: In 32 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTA was performed if feasible; if not, primary bypass grafting was done when feasible. All patients were followed until healing or for at least one year. Patients with worsening ulcers after PTA underwent bypass grafting. Clinical and angiographic factors influencing outcomes after PTA were sought by univariate and multivariate analysis. RESULTS: PTA was done in 25 of the 32 (78%) patients, and considered clinically successful in 13 (52%). After 1 year, the healing rate was 70% and the limb salvage rate 90%. Successful PTA was significantly associated with a higher post-PTA transcutaneous oxygen pressure (P = 0.03) and presence of at least one patent pedal vessel (P = 0.03) in the univariate analysis; only a patent pedal vessel was significant in the multivariate analysis. CONCLUSION: Primary PTA in diabetic patients with severe ischemic foot ulcers provides similar outcomes to usual results obtained in severe ischemia in absence of diabetes. The presence of one patent pedal vessel on arteriography before PTA is the best prognostic factor.

[Pseudo-aneurysms of the ascending aorta in patients previously operated for acute aortic dissection]. / Pseudo-anévrismes de l'aorte ascendante chez les patients déjà opérés d'une dissection aortique aiguë. Diagnostic, traitement.

Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.

Takayasu Arteritis and Pregnancy.

OBJECTIVE: To assess the relationship between Takayasu arteritis (TAK) and pregnancy outcome. METHODS: This study included 240 pregnancies in 96 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK and/or the 1994 Chapel Hill Consensus Conference nomenclature/criteria for vasculitis. We analyzed obstetric and maternal outcomes in women who were pregnant before and/or at the same time as or after TAK diagnosis. We assessed factors associated with complicated pregnancy. RESULTS: One hundred forty-two pregnancies occurred in 52 patients before TAK diagnosis (median age at pregnancy 26 years [interquartile range 23-30 years]), and 98 pregnancies occurred in 52 patients concomitant with or after TAK diagnosis (median age at pregnancy 28 years [interquartile range 26-31 years]). Pregnancies concomitant with or after TAK diagnosis had a 13-fold higher rate of obstetric complications compared to pregnancies before TAK diagnosis (odds ratio 13 [95% confidence interval 5-33], P < 0.0001). TAK was associated with a 40% frequency of obstetric complications, including preeclampsia/eclampsia (24 pregnancies [24%]), premature delivery (8 pregnancies [8%]), and intrauterine fetal growth restriction or death (5 pregnancies [5%]). Maternal complications of TAK occurred during 39% of pregnancies and included mainly new-onset or worsening hypertension (26 pregnancies [27%]). In multivariate analysis, smoking (odds ratio 6.15 [95% confidence interval 1.31-28.8]) and disease activity of TAK (a National Institutes of Health score of >1) (odds ratio 28.7 [95% confidence interval 7.89-104.7]) were independently associated with obstetric and maternal complications. CONCLUSION: TAK negatively affects pregnancy outcomes. Disease activity increases the risk of obstetric and maternal complications, mainly due to arterial hypertension.

Th1 and Th17 cytokines drive inflammation in Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK. METHODS: T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age- and sex-matched healthy control subjects. RESULTS: We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon-γ (IFNγ) and interleukin-17A (IL-17A). We demonstrated the presence of IFNγ-, IL-6-, and IL-17A-producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid-free patients with TAK (for IL-2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL-1 receptor, IL-17, and IL-23). CONCLUSION: The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.

Bacteriophages of lactobacilli.

Lactobacilli are members of the bacterial flora of lactic starter cultures used to generate lactic acid fermentation in a number of animal or plant products used as human or animals foods. They can be affected by phage outbreaks, which can result in faulty and depreciated products. Two groups of phages specific of Lactobacillus casei have been thoroughly studied. 1. The first group is represented by phage PL-1. This phage behaves as lytic in its usual host L. casei ATCC 27092, but can lysogenize another strain, L. casei ATCC 334. Bacterial receptors of this phage are located in a cell-wall polysaccharide and rhamnose is the main component of the receptors. Ca2+ and adenosine triphosphate (ATP) are indispensable to ensure the injection of the phage DNA into the bacterial cell. The phage DNA is double-stranded, mostly linear, but with cohesive ends which enables it to be circularized. The vegetative growth of PL-1 proceeds according to the classical mode. Cell lysis is produced by an N-acetyl-muramidase at the end of vegetative growth. 2. The second group is represented by the temperate phage phi FSW of L. casei ATCC27139. It has been shown how virulent phages originate from this temperate phage in Japanese dairy plants. The lysogenic state of phi FSW can be altered either by point mutations or by the insertion of a mobile genetic element called ISL 1, which comes from the bacterial chromosome. This is the first transposable element that has been described in lactobacilli. Lysogeny appears to be widespread among lactobacilli since one study showed that 27% of 148 strains studied, representing 15 species, produced phage particles after induction by mitomycin C. Similarly, 23 out of 30 strains of Lactobacillus salivarius are lysogenic and produce, after induction by mitomycin C, temperate phages, killer particles, or defective phages. Temperate phages have also been found in 10 out of 105 strains of Lactobacillus bulgaricus or Lactobacillus lactis after induction by mitomycin C. Phages so far studied of the latter 2 and closely related lactobacilli, either temperate or isolated as lytic, may be divided into 4 unrelated groups called a, b, c and d. Most of these phages are found in group a and an unquestionable relationship has already been shown between lytic phages and temperate phages that belong to this group. Lytic phage LL-H of L. lactis LL 23, isolated in Finland, is one of the most representative of those of group a and has been extensively studied on the molecular level.

Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?

BACKGROUND: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist. AIM: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials. METHODS: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen. RESULTS: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant. CONCLUSIONS: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology. CT Scan ARDS Study Group.

OBJECTIVE: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. MEASUREMENTS AND RESULTS: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17% and 58% respectively, and an excess lung tissue of 701+/-321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27% of the patients were characterized by "compression atelectasis," defined as a massive loss of aeration with no concomitant excess in lung tissue, and "inflammatory atelectasis," defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73% of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23% had diffuse attenuations evenly distributed in the two lungs, 36% had lobar attenuations predominating in the lower lobes, and 41% had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. CONCLUSIONS: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.

Regional distribution of gas and tissue in acute respiratory distress syndrome. II. Physiological correlations and definition of an ARDS Severity Score. CT Scan ARDS Study Group.

OBJECTIVES: (a) To assess whether differences in lung morphology observed in patients with adult respiratory distress syndrome (ARDS) are associated with differences in cardiorespiratory parameters, lung mechanics, and outcome. (b) To propose a new ARDS Severity Score to identify patients with a high mortality risk. DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early ARDS. MEASUREMENTS AND RESULTS: Cardiorespiratory parameters were measured using a Swan-Ganz catheter, the pressure-volume (PV) curve was measured using the gross syringe method, and fast spiral computed tomography (CT) was performed. Patients with diffuse attenuations (n = 16) differed from patients with lobar attenuations (n = 26) regarding: (a) mortality rate (75% vs. 42%, p = 0.05), (b) incidence of primary ARDS (82% vs. 50%, p = 0.03), (c) respiratory compliance (47 +/- 12 vs. 64 +/- 16 ml per cmH2O(-1) p = 0.04), and (d) lower inflexion point (8.4 +/- 2.0 vs. 4.6 +/- 2.0 cmH2O, p = 0.001). A third group of patients with patchy attenuations (n = 29) had a mortality rate of 41 %, a respiratory compliance of 56 +/- 18 ml per cmH2O(-1) and a lower inflexion point of 6.3 +/- 2.7 cmH2O. The bedside chest radiograph accurately assessed lung morphology in only 42% of the patients. In contrast to the scores based on the bedside chest radiograph, a new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters identified a subgroup of patients with a high mortality rate (> or = 60%). CONCLUSIONS: In patients with ARDS, differences in lung morphology are associated with differences in outcome and lung mechanics. A new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters accurately identified patients with the most severe forms of ARDS and a mortality rate above 60%.

Regional distribution of gas and tissue in acute respiratory distress syndrome. III. Consequences for the effects of positive end-expiratory pressure. CT Scan ARDS Study Group. Adult Respiratory Distress Syndrome.

OBJECTIVE: To determine whether differences in lung morphology assessed by computed tomography (CT) affect the response to positive end-expiratory pressure (PEEP). DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS). MEASUREMENTS AND RESULTS: Fast spiral thoracic CT was performed at zero end-expiratory pressure (ZEEP) and after implementation of PEEP 10 cmH2O. Hemodynamic and respiratory parameters were measured in both conditions. PEEP-induced overdistension and alveolar recruitment were quantified by specifically designed software (Lungview). Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung, characterized by a CT attenuation ranging between -900 and -800 HU in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume (gas + tissue) at functional residual capacity. PEEP-induced alveolar recruitment was greater in the lower lobes with "inflammatory atelectasis" than in the lower lobes with "mechanical atelectasis." Lung morphology as assessed by CT markedly influenced the effects of PEEP: in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension, whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations (compliant upper lobes and stiff lower lobes) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations. CONCLUSIONS: In patients with ARDS, the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury (primary versus secondary ARDS). The regional distribution of the loss of aeration and the type of atelectasis -- "mechanical" with a massive loss of lung volume, or "inflammatory" with a preservation of lung volume-- characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP.

Initial imaging assessment of severe blunt trauma.

OBJECTIVES: Total body computed tomography (CT) scan is increasingly used in traumatised patients, but the need for an initial rapid imaging assessment beforehand remains unknown. To address this problem, we assessed the value of an initial imaging assessment (chest X-ray, pelvic X-ray, abdominal ultrasonography) in severely traumatised patients in a prospective study. DESIGN AND SETTING: Prospective study of a cohort in a level 1 trauma centre of an university teaching hospital. PATIENTS AND INTERVENTIONS: 400 patients with severe blunt trauma. Within 30 min of arrival in the hospital, these patients underwent a rapid imaging assessment at the bedside, including chest and pelvic X-ray, and an abdominal ultrasonography. The decision taken for each imaging technique (chest drainage or thoracotomy, pelvic angiography, and laparotomy, respectively) was judged as appropriate or inappropriate. MEASUREMENTS AND RESULTS: Emergency chest drainage or thoracotomy was performed in 78 cases (78 appropriate), pelvic angiography in 8 cases (5 appropriate) and immediate laparotomy in 48 cases (47 appropriate). Emergency treatment was decided in 108 patients, and the decisions were considered appropriate in 392 (98%, 95% CI: 97%-99%) cases. Three variables (heart rate, systolic arterial pressure and Glasgow Coma Scale) were independent predictors of the need for an emergency decision, but among patients who had none of these criteria, 16% required an emergency decision. CONCLUSIONS: A simple and rapid initial imaging assessment enabled appropriate emergency decisions before further imaging assessment was performed. We recommend that every patient with severe blunt trauma receive this initial assessment.

Inhaled nitric oxide in acute respiratory failure: dose-response curves.

OBJECTIVE: To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure. DESIGN: Prospective randomized study. SETTING: A 14-bed ICU in a teaching hospital. PATIENTS: 6 critically ill patients with severe acute respiratory failure (lung injury severity score > or = 2.5) and pulmonary hypertension. INTERVENTIONS: 8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15-20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded. RESULTS: The administration of 100-2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease--25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb. CONCLUSION: In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100-2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Inhaled nitric oxide in acute respiratory distress syndrome with and without septic shock requiring norepinephrine administration: a dose-response study.

BACKGROUND: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). RESULTS: Eight patients with ARDS and without septic shock (PaO2 = 95 +/- 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 +/- 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P

[Natural history of arterial hypertension due to primary hyperreninism]. / Histoire naturelle d'une hypertension artérielle par hyperréninisme primaire.

This case report deals with an eight-year duration severe high renin hypertension and its consequences. In 1975, a 13 years old girl was found to have blood pressure (BP) levels of 240/150 mmHg with bilateral papilloedema. Hypokalemic alkalosis, a 45 mm Sokolow index (SI) and very high peripheral renin activity (PRA) were also noticed. Renal vein renin sampling (RVRS) suggested secretion from the left kidney but intravenous pyelography and renal arteriography were normal. BP levels were first controlled by triple treatment but rose one year later, despite adjunction of beta-blockers. High PRA was again found, but without hormonal gradient on a second RVRS. From 1977 to 1982, BP never fell to normal levels despite quadruple treatment. In 1982, a stage II optic fundus, a 58 mm SI and 2 g/day proteinuria are noticed, so that a new complete etiologic work up is undertaken in 1983: PRA is still high, with a dramatic acute BP fall after captopril and no gradient on a third RVRS, but intravenous pyelography, tomodensitometry and selective arteriography disclose a 4 cm diameter poorly vascularized tumour on the surface of the lower pole of the right kidney. BP levels are controlled for three months by captopril + chlorothiazide. The tumour is removed in january 1984. RVRS by direct peroperative punction indicates (a posteriori) hormonal secretion from the right kidney lower pole. Histologic examination and immunofluorescence with antirenin serum corroborate the juxtaglomerular origin of the tumour. Eighteen months later, BP is permanently normal, SI is 30 mm, and there is no proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)