BACKGROUND:Adjuvant chemotherapy improves survival of completely resected non-small cell lung cancer (NSCLC). However the regimen of choice is not yet defined. METHODS:The primary objective of this comparative, open, randomised multicentre trial is to compare two chemotherapy regimens (cisplatin/docetaxel versus cisplatin/gemcitabine) in the management of resected NSCLC with quality of life (QoL) evaluated at the end of treatment as the primary objective. The secondary objectives are to study the impact of these two chemotherapy regimens on overall and relapse free survival, hematological and non-hematological toxicities, and costs. The primary judgement criterion will be the assessment of end of treatment QoL by the standardised questionnaire, EORTC QLQ-C30. Secondary judgement criteria will be Qol measured by EORTC QLQ-LC13 and SF36, overall and relapse free survival, tolerance and costs. The number of subjects needed is 75 in each group, 150 in total, to detect a difference of 10 points on the EORTC QLC-C30 scores with a standard error of 20 points (alpha 0.05; power 80%). EXPECTED RESULTS:This trial will provide clinicians with data on the impact of two currently unexplored adjuvant chemotherapy regimens on quality of life, tolerance and costs in NSCLC.

The aim of the present study was to determine the risk factors and impact on outcome of blood transfusions following pneumonectomy for thoracic malignancies.A retrospective analysis of 432 consecutive patients was carried out, of whom 183 (42.4%) were transfused post-operatively. The associations between blood transfusions and 20 variables were assessed by univariate and multivariate analysis. Survival analysis included log-rank test and Cox regression model.Patient age, neoadjuvant treatment, completion pneumonectomy and extended procedures were independent predictors of transfusion. It was found that 30-day mortality increased significantly from 2.4% (no transfusion) to 10.9 and 21.9% (≤2 and >2 red blood cell packs, respectively). Blood transfusion was the strongest predictor of 30-day mortality (odds ratio (OR) 10; 95% confidence interval (CI): 3.7–27), respiratory failure (OR 19.2; 95% CI 7.4–49.4) and infectious complications (OR 3; 95% CI 1.5–6.2). In the 367 lung cancer patients, a significantly lower 5-yr survival was observed in univariate analysis of transfused patients (27.8±5.4%versus39.4±4.5%). In a Cox regression analysis, blood transfusion was no longer found to be significant.A dose-related correlation is suggested between blood transfusion and early mortality through an increase of infectious and respiratory complications. In contrast, blood transfusion had no independent adverse impact on long-term survival.

La chimiothérapie adjuvante à la chirurgie améliore la survie des cancers bronchiques non à petites cellules (CNAPC) complètement réséqués. L'objectif principal de cet essai multicentrique, comparatif, ouvert, randomisé, est de comparer deux schémas de chimiothérapie (cisplatine/docétaxel versus cisplatine/gemcitabine), dans la prise en charge du CNAPC réséqué, en matière d'impact sur la qualité de vie (QdV) évaluée à la fin du traitement. Les objectifs secondaires sont d'étudier l'impact de ces deux thérapeutiques sur la survie, les toxicités hématologiques et extra-hématologiques et les coûts. Le critère de jugement principal est représenté par la mesure de la QdV à l'aide d'un questionnaire standardisé, l'EORTC QLQ-C30. Les critères de jugement secondaires sont multiples : QdV mesurée par l'EORTC QLQ-LC13 et le SF36, survies globales et sans progression, profil de tolérance et coûts. Le nombre de sujets nécessaires est de 75 sujets par groupe, 150 au total (hypothèses : alpha 0.05, puissance 80 %, différence attendue en terme de score EORTC QLQ-C30 de 10 points, écart-type de 20 points). Cet essai fournira aux cliniciens des données sur l'impact sur la qualité de vie, la tolérance et les coûts de deux combinaisons de chimiothérapie adjuvante non explorées à ce jour dans les CNAPC. Adjuvant chemotherapy improves survival of completely resected non-small cell lung cancer (NSCLC). However the regimen of choice is not yet defined. The primary objective of this comparative, open, randomised multicentre trial is to compare two chemotherapy regimens (cisplatin/docetaxel versus cisplatin/gemcitabine) in the management of resected NSCLC with quality of life (QoL) evaluated at the end of treatment as the primary objective. The secondary objectives are to study the impact of these two chemotherapy regimens on overall and relapse free survival, haematological and non-haematological toxicities, and costs. The primary judgement criterion will be the assessment of end of treatment QoL by the standardised questionnaire, EORTC QLQ-C30. Secondary judgement criteria will be Qol measured by EORTC QLQ-LC13 and SF36, overall and relapse free survival, tolerance and costs. The number of subjects needed is 75 in each group, 150 in total, to detect a difference of 10 points on the EORTC QLC-C30 scores with a standard error of 20 points (alpha 0.05; power 80%). This trial will provide clinicians with data on the impact of two currently unexplored adjuvant chemotherapy regimens on quality of life, tolerance and costs in NSCLC.

ObjectiveTo evaluate the effects of a 48-hr neuromuscular blocking agents (NMBA) infusion on gas exchange over a 120-hr time period in patients with acute respiratory distress syndrome. DesignMultiple center, prospective, controlled, and randomized trial. SettingFour adult medical or mixed medical-surgical intensive care units. PatientsA total of 56 patients with acute respiratory distress syndrome with a Pao2/Fio2 ratio of <150 at a positive end-expiratory pressure of ≥5 cm H2O. InterventionsAfter randomization, patients received either conventional therapy without NMBA (control group) or conventional therapy plus NMBA for the next 48 hrs. The initial ventilator mode was volume-assist/control. The ventilator remained on assist-control mode throughout the initial 48-hr period in both groups. Tidal volume was 6–8 mL/kg ideal body weight. Measurements and Main ResultsWhen analyzed for the entire 120 hrs, there was a significant effect of the NMBA on the course of Pao2/Fio2 ratio (p = .021). Separate comparisons at each time point indicated that patients randomized to the NMBA group had a higher Pao2/Fio2 at 48, 96, and 120 hrs after randomization. Moreover, a decrease of positive end-expiratory pressure (p = .036) was only found in the NMBA group. Two-way repeated-measures analysis of variance exhibited a decrease in positive end-expiratory pressure over time (p = .036). Concerning short-term effects, there was no modification of Pao2/Fio2 ratio 1 hr after randomization in either group. Only one patient (from the control group) developed pneumothorax. ConclusionsUse of NMBA during a 48-hr period in patients with acute respiratory distress syndrome is associated with a sustained improvement in oxygenation.

L’héparinisation du circuit extracorporel en hémodialyse est particulièrement difficile à mener chez les patients à risque hémorragique. Des doses excessives risquent de provoquer des saignements et des doses insuffisantes peuvent entraîner une coagulation du circuit. Il est donc fondamental de bien choisir la dose initiale d’héparine et de l’adapter au cours de la séance. Si l’observation clinique des lignes et du dialyseur est réalisée de façon habituelle, aucun paramètre biologique n’est utilisé actuellement. Le délai d’obtention d’un résultat de laboratoire est trop long pour permettre une modification rapide et efficace de la dose d’anticoagulant. Un appareil de mesure délocalisé, c’est-à-dire utilisable au sein du service pourrait répondre à cette attente. La société Gamida distribue 2 appareils de la marque Hémochron® qui permettent de mesurer un temps de coagulation sur sang total : l’ACT (Activated Clotting Time). Nous avons testé chacun de ces 2 appareils, tant au niveau de leur manipulation qu’au niveau des résultats rendus. Onze patients ont été inclus dans cette étude. Des mesures régulières de l’ACT ont été réalisées en cours de séance simultanément avec chacun des 2 appareils. Les résultats obtenus ont été comparés et mis en parallèle avec les mesures du TCA et de l’héparinémie rendues par le laboratoire. Les 2 appareils ont rendu des résultats satisfaisants mais c’est l’évaluation pratique qui a orienté nos conclusions. L’aspect économique de ce type de matériel est en cours d’évaluation.

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

Objectives: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). Materials and methods: The medical records of all patients who underwent lung resection for a patholgical stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patient (430 males and 81 females) whose age averaged 63 +/- 10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS), Lymph node dissection was performed in all cases. Results: There were significantly more females (P = 0.01) and adenocarcinoma (P = 0.02) in the VATS group (n = 110) when compared to the open group (n = 405). Tumour size averaged 4 +/- 2 cm in the open group and 3 +/- 2 cm in the VATS group (P = 0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P = 0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%: P = 0.64). Estimated Kaplan-Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8-68.7%) vs. 62.9% (CIL: 51.4-74.4%), respectively (P = 0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3-72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7-65.9%) for the period from 1993 to 1999 (P = 0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two group. Conclusions: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC (C) Elsevier Science B.V. All rights reserved.

Background: The early stage of post-transplant obliterative bronchiolitis (013) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB.Methods: Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA).Results: Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 164 days and 307 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 323 and 152 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups.Conclusions: These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and, sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.

To investigate whether tumour necrosis factor alpha (TNFalpha) plays a role in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinaemia (HCV-MC), we measured soluble TNFalpha and its soluble p55 (sTNFR1) and p75 (sTNFR2) receptors in the serum of patients with HCV-MC. TNFalpha, sTNFR1 and sTNFR2 were measured in the serum of 32 patients with HCV-MC, 18 patients with hepatitis C without MC (HCV) and 18 healthy volunteers, using specific immunoassays. Correlations between clinical and biological parameters and the concentrations of TNFalpha and sTNFRs were established by studying detailed clinical records of the 32 HCV-MC patients. Although higher, TNFalpha levels were not significantly different in HCV-MC patients compared with healthy or HCV controls. sTNFR1 and sTNFR2, however, were significantly higher in HCV-MC compared with controls or with HCV patients, and higher concentrations of sTNFR1 and sTNFR2 were observed in patients with severe visceral vasculitis, compared with patients with limited purpura. sTNFR1 concentrations positively correlated with fibrinogen levels but TNFalpha, sTNFR1 and sTNFR2 did not correlate with other biological parameters such as rheumatoid factor concentrations, CH50 or C4 values. These data suggest a role for TNFalpha in the pathogenesis of the immune complex-mediated vasculitis associated with HCV-MC.

BACKGROUND:Long-term results of the surgical treatment of stage I non-small cell lung cancer (NSCLC) are disappointing.METHODS:Univariate and multivariate analyses were conducted on 515 consecutive lung resections for stage I NSCLC performed from 1990 to 1999 and identified by reviewing a database into which data were entered prospectively. Tumors were staged as stages IA (n = 147) and IB (n = 348) according to the 1997 UICC (Union Internationale Contre le Cancer) pTNM classification.RESULTS:Operative mortality rates were 6.2%, 5.3%, 2.3%, and 0% for pneumonectomy, bilobectomy, lobectomy, and lesser resections, respectively. Overall survival rate was 61.1% (55.8% to 66.5%) at 5 years. Univariate analysis identified three significant adverse prognosticators: arteriosclerosis as comorbidity, pathologic T2 status, and blood vessel invasion. Male sex (p = 0.056) and performance of pneumonectomy (p = 0.057) were at the threshold of statistical significance. At multivariate analysis, three independent prognosticators entered the model: arteriosclerosis, blood vessels invasion, and performance of pneumonectomy.CONCLUSIONS:Long-term survival of patients with completely resected stage I NSCLC was adversely influenced in a relatively balanced way by factors related to the clinical status of the patient, to the tumor, and to the treatment.

BACKGROUND:In some patients with acute respiratory distress syndrome, the prone position is able to improve oxygenation, whereas in others it is not. It could be hypothesized that the more opacities that are present in dependent regions of the lung when the patient is in the supine position, the better the improvement in oxygenation is observed when the patients are turned prone. Therefore, we conducted a prospective study to identify computed tomographic scan aspects that could accurately predict who will respond to the prone position.METHODS:We included 46 patients with acute respiratory distress syndrome (31 responders and 15 nonresponders). Computed tomographic scan was performed in the 6-h period preceding prone position. Blood gas analyses were performed before and at the end of the first 6-h period of prone position.RESULTS:Arterial oxygen partial pressure/fraction of inspired oxygen increased from 117 +/- 42 (mean +/- SD) in the supine position to 200 +/- 76 mmHg in the prone position (P < 0.001). There were 31 responders and 15 nonresponders. There was a vertebral predominance of the opacities (P < 0.0001). However, there was no difference between responders and nonresponders. When only the amount of consolidated lung located under the heart was evaluated, there was more consolidated tissue under the heart relative to total lung area in nonresponders than in responders (P = 0.01).CONCLUSIONS:There are no distinctive morphologic features in the pattern of lung disease measured by computed tomographic scanning performed with the patient in the supine position that can predict response to the prone position.

. Objective : To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 µg/kg per minute and 16 µg/kg per minute in ARDS patients responding to and receiving inhaled NO (iNO) and presenting septic shock requiring norepinephrine, while no difference was observed in a previous trial including iNO responders and nonresponders. Design : Prospective, cohort study. Setting : Adult medico-surgical intensive care unit of a university hospital. Patients : Fifteen patients with ARDS receiving and responding to iNO (10 ppm) and presenting septic shock requiring norepinephrine (mean 0.5±0.45 µg/kg per minute, range 0.08– 2.08). Interventions : The protocol consisted of two consecutive phases in a fixed order: continuous intravenous infusion of AB 5 µg/kg per minute for 30 min, and continuous intravenous infusion of AB 16 µg/kg per minute for 30 min. Measurements and main results : AB 5 µg/kg per minute significantly increased PaO 2 /FiO 2 ( P <0.05) compared with iNO alone [160 (range 77–450) mmHg vs 122 (range 70–225) mmHg]. AB 16 µg/kg per minute produced a greater increase of PaO 2 /FiO 2 ( P <0.05) when compared with 5 µg/kg per minute [227 (range 84–501) mmHg]. AB did not improve shunt at any dose regimen. AB produced an increase in mean pulmonary arterial pressure (MPAP) from 22±5 to 25±4 mmHg ( P <0.03). MPAP did not significantly increase between the two doses. Pulmonary vascular resistances and other haemodynamic and respiratory parameters were not affected by almitrine bismesylate. Conclusions : These results suggest that it is possible to obtain a further improvement in oxygenation by increasing AB infusion rate in ARDS patients iNO responders receiving norepinephrine. Due to the potential deleterious effects of AB, this strategy should be used in the most severely hypoxaemic patients.

Background Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation. Methods During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP. Results Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia. Conclusion Ventilator-associated pneumonia does not appear to be an independent risk factor for death.

Objectives: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. Methods: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (range 20-60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). Results: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51 %) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). Conclusions: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems 'acceptable', the morbidity rate, however, is high. (C) 2001 Elsevier Science B.V. All rights reserved.

To assess the influence of the timing of nephrology referral on the short- and long-term outcome of hemodialysis patients, we retrospectively studied 309 patients who had end-stage renal failure and entered the chronic hemodialysis program in Sainte-Marguerite University Hospital between January 1, 1989, and December 31, 1996. We excluded from the analysis five patients without available data on referral pattern and 34 patients with irreversible acute renal failure. Of the remaining 270 patients, 177 patients (58%) had an early referral (ER) 16 or more weeks before the start of dialysis, and 93 patients (31%) had a late referral (LR) of less than 16 weeks before dialysis. Short-time morbidity (initial emergent dialysis, pulmonary edema, severe hypertension, temporary vascular access placement for first dialysis, prolonged initial hospitalization) was significantly more frequent in LR patients. Long-term evolution (mean follow-up, 26.5 ± 26 months) did not differ between the two groups. The number of days of hospitalization per patient-year at risk beyond the third month was 21.5 ± 33.7 days for ER and 21.1 ± 36 days for LR patients. Survival analysis showed no difference between the two groups: 3-month survival rates were 96% in both groups, 1-year survival rates were 90% in the ER and 89% in the LR group, and 5-year survival rates were 52% in the ER and 56% in the LR group. In a Cox hazards regression model, referral pattern was not associated with a greater risk for death. In conclusion, delayed nephrology referral generated strikingly greater initial morbidity, but long-term outcome of hemodialysis patients was not modified by delayed nephrological care.

The combination of inhaled nitric oxide with almitrine bismesylate has been proposed for the management of acute respiratory distress syndrome in order to divert pulmonary blood flow away from poorly ventilated toward well-ventilated areas. The aims of this prospective and comparative study were to: 1) confirm the beneficial effects on oxygenation of this association; 2) evaluate the haemodynamic effects of this association; and 3) evaluate the influence of noradrenaline (a nonspecific vasoconstrictor) on the modification of gas exchange related to inhaled NO and/or almitrine bismesylate.Forty-one sedated paralysed and ventilated patients were investigated. Haemodynamic and blood gas measurements were performed in a fixed order: baseline; inhalation of NO for 30 min.; intravenous infusion of almitrine bismesylate; and concomitant administration of inhaled NO and almitrine bismesylate.Inhaled NO and almitrine bismesylate increased arterial oxygen tension (Pa,O-2)/inspiratory oxygen fraction (FI,O-2) (p<0.001). The association of inhaled NO with almitrine bismesylate resulted in a dramatic improvement in Pa,O-2/FI,O-2 (p<0.0001 versus almitrine bismesylate, p<0.05 versus inhaled NO). In patients receiving noradrenalin (n=19), almitrine bismesylate had no effect on oxygenation.The present study confirmed that the combination of inhaled NO with almitrine bismesylate improved oxygenation, and demonstrated that almitrine bismesylate has no effect on oxygenation in patients receiving noradrenalin.

It has been suggested that the increase in PO(2) observed with nitric oxide (NO) should be enhanced by the addition of a vasoconstrictor agent. The vasoconstrictor used in combination with NO should mimic or enhance hypoxic vasoconstriction. The aim of this study was to evaluate the respiratory and hemodynamic effects of norepinephrine (a nonspecific vasoconstrictor), almitrine bismesylate (a specific pulmonary vasoconstrictor), and inhaled NO, alone or together. During a 6-mo period, 16 patients presenting with ARDS were prospectively investigated. On inclusion, no patient was receiving cardiovasoactive drugs. The protocol consisted of seven consecutive phases: baseline, norepinephrine (in order to obtain a 3 mm Hg rise in mean pulmonary arterial pressure [Ppa]), almitrine bismesylate (16 micrograms/kg/min), inhaled NO (20 ppm delivered during inspiration), norepinephrine + inhaled NO, almitrine bismesylate + inhaled NO, almitrine bismesylate + norepinephrine + inhaled NO. General factorial analysis of variance showed that inhaled NO and almitrine bismesylate increased oxygenation (p < 0.0001). Norepinephrine had no effect on oxygenation. A synergistic effect between inhaled NO and almitrine bismesylate was found (p < 0.05), whereas norepinephrine did not affect the response to inhaled NO. Nitric oxide produced a significant decrease in Ppa and pulmonary vascular resistances (PVRI) (p < 0.0001). Both almitrine bismesylate and norepinephrine induced an increase in Ppa (p < 0.0001). Norepinephrine increased PVRI (p < 0.002), whereas almitrine bismesylate had no effect on PVRI. The present results support the hypothesis that a selective pulmonary vasoconstrictor enhances the increase in oxygenation induced by inhaled NO, whereas norepinephrine attenuates this effect.

UNLABELLED:Hypoxia-related pulmonary vasoconstriction enhanced by norepinephrine could be deleterious in patients with the acute respiratory distress syndrome (ARDS) and sepsis. A prospective study compared the effects of nitric oxide on cardiorespiratory parameters, including the evaluation of right ventricular function in patients with ARDS and sepsis who were receiving or not receiving norepinephrine.METHODS:During a 15-month period, 27 patients with ARDS and sepsis were prospectively investigated (group 1: 15 patients not receiving norepinephrine; group 2: 12 patients receiving norepinephrine). Right ventricular ejection fraction was measured by thermodilution. After baseline measurements, nitric oxide was administered at increasing inspiratory concentrations.RESULTS:The ratio of oxygen tension in arterial blood to the fractional concentration of oxygen in inspired gas increased in the two groups. After logarithmic transformation of the data, an analysis of variance was performed that did not show any difference between the two groups. A dose-dependent decrease in mean pulmonary arterial pressure was observed in the two groups. This decrease and the increase in right ventricular ejection fraction induced by inhaled nitric oxide were more marked when patients received norepinephrine (P < 0.0001).CONCLUSION:Norepinephrine did not influence the beneficial effects of inhaled nitric oxide administered to patients with ARDS and sepsis on oxygenation.

OBJECTIVE:To asses the diagnostic accuracy of endoscopic ultrasonography (EUS) for the local and regional staging of esophageal cancer, and its possible alteration resulting from the performance of preoperative chemoradiation.METHODS:Prospective study of 85 consecutive patients with esophageal cancer evaluated by EUS and operated between January 1992 and December 1995. 28 of these patients had received previous induction therapy. In all cases, EUS examination was performed by the same physician not informed about the results of previous morphological explorations. Histopathological analysis of all specimens was performed by the same pathologist, not informed about the results of the EUS. Data were collected by another independent observer.RESULTS:EUS examination resulted in incomplete staging in 8 patients (9.5%) with severe stenosis precluding endoscope passage. The accuracy, specificity and sensibility of EUS in detecting the depth of esophageal involvement (T0-2 vs T3-4) were 82.3%, 78% and 86% respectively, and 72%, 70% and 73% respectively for the lymph node metastasis. The overall accuracy of EUS in identifying the preoperative stage was 67% with a clear-cut alteration when patients had received induction therapy (61% vs 72%). On the other hand, 7(64%) of the 11 patients thought to have a complete response at endosonography had no residual tumor.CONCLUSION:EUS provides precise information for the preoperative identification of locally advanced esophageal tumor, even after induction therapy. The latter alters the diagnostic accuracy of EUS, although complete responders could be identified in two-thirds os cases.