Melanoma and rituximab: an incidental association?

Rituximab is an anti-CD20 monoclonal antibody increasingly used in haematology and rheumatology, but also in internal medicine and dermatology. It has a good tolerance profile without known increased risk of cancer. We report a case of nodular melanoma with a 4.8 mm Breslow thickness that appeared after 2 years of rituximab in a 45-year-old patient with non-Hodgkin lymphoma. Fifteen additional rituximab-associated melanoma cases in 13 patients have been identified in the literature and in the EudraVigilance database. These patients were treated for various indications and had melanomas, often aggressive, initially diagnosed at a metastatic stage in 31% of cases. Our work raises the question of rituximab accountability in melanoma onset in these immunosuppressed patients. A dermatological monitoring seems necessary in patients treated with rituximab, especially in case of risk factors for melanoma. In case of individual melanoma history, the benefit/risk ratio of initiating rituximab therapy should be carefully assessed.

[Description of medicosocial profiles of pharmacodependent subjects consulting addictology centres using a computerized database]. / Description de profils médicosociaux de sujets pharmacodépendants consultant en addictologie à partir d'une base de données informatique.

INTRODUCTION: Lots of similar vulnerabilities to substance use disorders are described in the literature: clinical, genetics, family, environment, etc. Although, when we follow up patients, we know perfectly well that there are also differences due to the substance mainly causing addiction. But we found very little research on the differences between various substance use disorders according to the substance mainly causing dependence. HYPOTHESIS: Our main hypothesis was that significant differences do not exist in medical and social data between patients with substance use disorders according to the substance mainly used. We expected to find significant differences between illegal substance use disorders (opiates, cocaine, cannabis) and legal substance use disorders (BZD, alcohol). OBJECTIVE: Our study aimed to identify differences between patients with substance related disorders in medical and social data according to the main addictive substance. MATERIAL AND METHOD: A specific software has been created by the CEIP and the Department of Addictology of Nantes University Hospital. Anonymous data were gathered and all patients gave their written consent. This database has been declared to CNIL (number 1350706). All data have been directly collected by the physician during medical consultation. The following data were recorded during the first medical examination: age, sex, illicit substance use, prior criminal record or psychiatric disorders, prior addictive behaviours among relatives and/or friends, family history (divorce, separation, abandonment). Other data were gathered prospectively: socioprofessional insertion, marital status, drug prescriptions (time and duration). RESULTS: We found significant differences in social (age, sex) and medical data (prior psychiatric disorders) between patients according to the substance causing dependence. We identified five profiles depending on the substance: cannabis, cocaine, heroin, alcohol and benzodiazepine. DISCUSSION: We clearly identified different types of patient's profiles according to substances mainly causing addiction. These differences can modify our strategies of prevention and treatment, so as to meet patients' needs better.

Treatment of cachexia with recombinant growth hormone in a patient before lung transplantation: a case report.

OBJECTIVES: To describe the effects of recombinant human growth hormone (rhGH) in a severely malnourished patient before lung transplantation. DESIGN: Case study. SETTING: Intensive care unit. PATIENTS: A 38-yr-old severely malnourished (body mass index, 15.1 kg/m2) woman (receiving prednisone) with bronchiolitis obliterans evolving during 10 yrs presented with end-stage lung disease and required continuous noninvasive mechanical ventilation. INTERVENTIONS: Two courses of 35 days of 16 IU/day (0.42 IU/kg/day) rhGH administered subcutaneously, with an interruption of 5 wks between the two courses of rhGH. MEASUREMENTS AND MAIN RESULTS: Weight gain of 14.7% and 12.8% fat-free mass, as measured by 50-kHz bioelectrical impedance analysis, during treatment during a 3.5-month period. Nitrogen excretion decreased from 23.7 g/day before treatment to 8.0 g/day while receiving rhGH. Improvement of pulmonary function was also noted and allowed discharge of the patient from the hospital after the second course of rhGH. She underwent successful lung transplantation 2 months later and reached 48.8 kg of body weight 6 months later. CONCLUSIONS: rhGH treatment is a possible strategy that could be used with malnourished patients who are awaiting lung transplantation to improve the nutritional status and respiratory muscle function to prevent recurring respiratory infection and postoperative complications favored by malnutrition and possibly to decrease the length of hospital stay.

Activation of human macrophages by mechanical ventilation in vitro.

Positive-pressure mechanical ventilation supports gas exchange in patients with respiratory failure but is also responsible for significant lung injury. In this study, we have developed an in vitro model in which isolated lung cells can be submitted to a prolonged cyclic pressure-stretching strain resembling that of conventional mechanical ventilation. In this model, cells cultured on a Silastic membrane were elongated up to 7% of their initial diameter, corresponding to a 12% increase in cell surface. The lung macrophage was identified as the main cellular source for critical inflammatory mediators such as tumor necrosis factor-alpha, the chemokines interleukin (IL)-8 and -6, and matrix metalloproteinase-9 in this model system of mechanical ventilation. These mediators were measured in supernatants from ventilated alveolar macrophages, monocyte-derived macrophages, and promonocytic THP-1 cells. Nuclear factor-kappaB was found to be activated in ventilated macrophages. Synergistic proinflammatory effects of mechanical stress and molecules such as bacterial endotoxin were observed, suggesting that mechanical ventilation might be particularly deleterious in preinjured or infected lungs. Dexamethasone prevented IL-8 and tumor necrosis factor-alpha secretion in ventilated macrophages. Mechanical ventilation induced low levels of IL-8 secretion by alveolar type II-like cells. Other lung cell types such as endothelial cells, bronchial cells, and fibroblasts failed to produce IL-8 in response to a prolonged cyclic pressure-stretching load. This model is of particular value for exploring physical stress-induced signaling pathways, as well as for testing the effects of novel ventilatory strategies or adjunctive substances aimed at modulating cell activation induced by mechanical ventilation.

[Uroselectivity of alpha-1 antagonism in the treatment of benign prostatic hypertrophy: on the pharmacologic concept of the clinical approach]. / Urosélectivité de l'antagonisme alpha-1 dans le traitement de l'hypertrophie bénigne de la prostate: du concept pharmacologique à l'approche clinique.

Benign prostatic hyperplasia is the most common cause of voiding dysfunction in men. It becomes symptomatic from the fifth decade of life and needs treatment in 50 per cent of patients. Hyperplastic prostatic tissue and the smooth involuntary sphincter have a high density of alpha 1-adrenoceptors, thus alpha 1-blockers can decrease sphincter tone and reduce the tension exerted by the prostatic muscular component. Attempts have been made to find alpha 1-antagonists that have a selective effect on the prostate (alfuzosin), are long acting (tamsulosin, terazosin, doxazosin) or present specificity on the alpha 1A prostatic adrenoceptors (tamsulosin), in order to maintain efficacy without affecting blood pressure. Finasteride, a 5 alpha-reductase inhibitor without hypotensive side-effect may be more effective in men with a predominantly glandular component to their benign hyperplasia or with very large prostate glands, but has a longer onset of action and produces more adverse sexual effects. Thus, alpha-1 antagonists can be considered as an appropriate treatment option in patients with troublesome symptoms of BPH and who have not developed serious complications indicating surgery.

Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences.

BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. METHODS: In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.

[Acute myocardial infarct in Switzerland: results from the PIMICS Heart Infarct Register. PIMICS Project (Prospective Ischemia Myocardial Infarction Captopril Survey)]. / Der akute Myokardinfarkt in der Schweiz: Resultate aus dem PIMICS-Herzinfarkt-Register. PIMICS-Projekt (Prospective Ischemia Myocardial Infarction Captopril Survey).

The aim of the PIMICS project was to create, for the first time in Switzerland, a registry of data concerning epidemiology and therapy in patients hospitalised for acute myocardial infarction covering all regions of the country. During 1995/96 73 Swiss hospitals of all categories took part in the PIMICS project. The ratio between males and females in the 3877 registered patients was 2.6:1 (2791 men vs. 1086 women). Female patients were significantly older than males (70.4 +/- 12.0 years vs. 63.4 +/- 12.6 years; p < 0.0001). The prevalence of risk factors differed between men and women: significantly more women had hypertension or diabetes, whereas smoking was more prevalent in males. The median delay between onset of symptoms and arrival at the hospital was 5.5 hours. Thrombolysis and primary angioplasty were more frequently performed in men (40.4% vs. 31.2% in women, p < 0.0001, and 5.7% in men vs. 3.5% in women, p = 0.005 respectively). During the acute phase males were treated more frequently with betablockers. The overall in-hospital mortality was 9.1%. It was significantly higher in female patients (13.5% vs. 7.4% in men; p < 0.0001) and in patients with reinfarction (14.5% vs. 7.1%; p < 0.0001). The mean hospital stay was 12.6 +/- 5.3 days. Only 7.7% of all patients with acute myocardial infarction were discharged within 6 days. At discharge, 51.7% were treated with betablockers and 69.3% with aspirin; 44.8% received ACE-inhibitors and only 13.8% lipid-lowering drugs. Follow-up measures such as coronary angiography and/or angioplasty or bypass surgery were performed significantly more often in males (45.0% vs. 32.9%; p < 0.0001). Likewise, men were more frequently assigned to a rehabilitation program than women (38.2% vs. 32.9%; p = 0.0004). The pre-hospital delay in patients with acute myocardial infarction remains too long. Primary and secondary prevention should be intensified in high risk groups, particularly in females. Thrombolysis and primary angioplasty as mainstays of treatment in acute myocardial infarction are generally used too sparingly, especially in women. With such measures the hospital stay could be shortened further.

Effects of the prone position on gas exchange and hemodynamics in severe acute respiratory distress syndrome.

OBJECTIVES: To address the following issues regarding the use of prone position ventilation in patients with severe acute respiratory distress syndrome (ARDS): a) response rate; b) magnitude and duration of improved oxygenation in responders during a 12-hr trial and the consequences of returning to the supine position; c) effects of the prone position on gas exchange and hemodynamics; d) consequences of oxygenation in nonresponders; and e) effects of repeated prone position trials. DESIGN: Prospective, nonrandomized interventional study. SETTING: Medical intensive care unit, university tertiary care center. PATIENTS: Nineteen consecutive, mechanically ventilated patients (age 45+/-20 yrs, mean+/-SD) with ARDS and severe hypoxemia, defined as PaO2/FiO2 of < or = 150 with FiO2 of > or = 0.6 persisting for < or =24 hrs, and a pulmonary artery occlusion pressure of <18 mm Hg. INTERVENTIONS: Patients were turned prone for 2 hrs. Nonresponders were returned supine, but responders were maintained prone for 12 hrs before being returned to the supine position. The procedure was repeated on a daily basis in all patients, until inclusion criteria were no longer met or the patients died. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, blood gas, and gas exchange measurements were performed at the following time points: a) baseline supine; b) after 30 mins prone; and c) after 120 mins prone. Additional measurements for nonresponders were taken after 30 mins supine. For responders, additional measurements were taken after 12 hrs prone and 30 mins supine. Patients were considered responders if an increase in PaO2 of > or = 10 torr (> or =1.3 kPa), or increase in the PaO2/FiO2 ratio of >20 occurred within 120 mins. Eleven (57%) patients responded to the prone position. There was no difference in initial baseline parameters between responders and nonresponders. After 30 mins, the prone position in responders increased PaO2 and decreased calculated venous admixture (Qva/Qt). This improvement was the maximal obtained, and was maintained throughout the 12-hr prone period. After 12 hrs prone, mean FiO2 had been lowered from 0.85+/-0.16 to 0.66+/-0.18 (p < .05). Thirty minutes after the patients were returned supine, PaO2, PaO2/FiO2, and Qva/Qt were not different from 12-hr prone values, and were improved in comparison with baseline supine values. There was no worsening of gas exchange or hemodynamics in nonresponders. After the initial trial, a total of 28 additional episodes of prone position ventilation were performed in nine of the 19 patients. Of the 24 additional episodes in the responders, there was a response in 17 (71%) of 24 episodes. In the four additional episodes in nonresponders, there was a response in only one (25%) of four episodes. Response was accompanied by the same beneficial effects on gas exchange and Qva/Qt and absence of effect on hemodynamics as in the initial trial. There was no worsening in gas exchange or hemodynamics in nonresponder trials. CONCLUSIONS: Based on the data from this study, the prone position can improve oxygenation in severely hypoxemic ARDS patients without deleterious effects on hemodynamics. This beneficial effect does not immediately disappear on return to the supine position. In our patients, an absence of response to this technique was not accompanied by worsening hypoxemia or hemodynamic instability. Repeated daily trials in the prone position should be considered in the management of ARDS patients with severe hypoxemia.

Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that prone position ventilation, nitric oxide, and almitrine bismesylate, each acting by a different mechanism to improve arterial oxygenation, could exert additive beneficial effects when used in combination in patients with severe acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonrandomized, interventional study. SETTING: Medical and surgical intensive care units at a university tertiary care center. PATIENTS: Twelve patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of < or = 150 and FIO2 of > or = 0.6, with pulmonary artery occlusion pressure of < 18 mm Hg. INTERVENTIONS: Inhaled nitric oxide (20 parts per million for 15 mins) in the supine and prone position, and intravenous almitrine bismesylate while prone (1 mg/kg/hr for 60 mins), alone or combined with nitric oxide. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, blood gas, and gas exchange measurements were performed at sequential time points as follows: a) baseline supine; b) nitric oxide in the supine position; c) after return to baseline supine; d) after 30 mins prone; e) after 120 mins prone; f) nitric oxide while prone; g) after return to baseline prone; h) almitrine bismesylate prone; and i) nitric oxide and almitrine bismesylate combined, for 15 mins prone. Patients were considered responders to the prone position if a gain in PaO2 of > or = 10 torr (> or = 1.3 kPa) or a gain in the PaO2/FIO2 ratio of > or = 20 was observed. Seven patients (58%) responded to being turned prone. Compared with supine baseline conditions, nitric oxide and supine position increased arterial oxygen saturation from 89 +/- 1 (SD)% to 92 +/- 3% (p < .05) and nitric oxide plus prone position increased arterial oxygen saturation (94 +/- 3% vs. 89 +/- 4%, p < .05) and decreased the alveolar-arterial oxygen difference from 406 +/- 124 torr (54 +/- 15 kPa) to 387 +/- 108 torr (51 +/- 14 kPa) (p < .05). Almitrine bismesylate increased PaO2/FIO2 vs. baseline (122 +/- 58 vs. 84 +/- 21, p < .05). Almitrine bismesylate decreased the alveolar-arterial oxygen difference vs. baseline from 406 +/- 124 torr (53.9 +/- 16.5 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) and vs. nitric oxide and supine position from 406 +/- 111 torr (53.9 +/- 14.7 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) (p < .05). Prone position alone did not improve oxygenation. However, the combination of nitric oxide and almitrine bismesylate increased PaO2/FIO2 vs. nitric oxide supine and nitric oxide prone conditions (147 +/- 69 vs. 84 +/- 25 and 91 +/- 18, respectively; p < .05). In patients responding to the prone position (n = 7), combining nitric oxide and almitrine bismesylate led to further improvement in PaO2 compared with the prone position alone, with PaO2 increasing from 78 +/- 12 torr (10.3 +/- 1.6 kPa) to 111 +/- 55 torr (14.7 +/- 7.3 kPa) (p < .05), which was not the case when either nitric oxide or almitrine bismesylate was added separately. Heart rate and cardiac output were increased by almitrine bismesylate compared with all other measurements. Mean pulmonary arterial pressure was decreased by nitric oxide (27 +/- 7 vs. 30 +/- 7 mm Hg nitric oxide supine vs. baseline supine and 29 +/- 7 vs. 33 +/- 8 mm Hg nitric oxide prone vs. baseline prone, p < .05) and increased by almitrine bismesylate (36 +/- 9 vs. 30 +/- 7 mm Hg baseline supine, 27 +/- 7 mm Hg nitric oxide supine, 33 +/- 8 mm Hg baseline prone, and 29 +/- 7 mm Hg nitric oxide prone; p < .05). The increase in mean pulmonary arterial pressure was totally abolished by nitric oxide (31 +/- 5 vs. 36 +/- 9 mm Hg, p < .05). Minute ventilation, respiratory system compliance, physiologic deadspace, and PaCO2 remained unchanged. CONCLUSION: In ARDS patients with severe hypoxemia, arterial oxygenation can be improved by combining the prone position, nitric oxide, and almitrine bismesylate, without deleterious effects.

Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange.

BACKGROUND: In patients with primary pulmonary hypertension who respond to vasodilators acutely, survival can be improved by the long term use of calcium channel blockers. However, testing for such a response with calcium channel blockers or prostacyclin (PGI2) may cause hypotension and adversely affect gas exchange. Nitric oxide (NO), which does not have these effects, could be a better test agent. METHODS: NO (10, 20, and 40 ppm for 15 minutes), PGI2 (1-->10 ng/kg/min), and oral nifedipine (10 mg, then 20 mg/h) were administered sequentially to 10 patients after determination of the 24 hour spontaneous variability of their pulmonary and systemic mean arterial pressures. Patients were considered responders if the mean pulmonary artery pressure or pulmonary vascular resistance decreased by 20% or more. RESULTS: Six patients (60%) responded to all three agents, and three to none of the agents. One patient responded to PGI2 only. In those who responded to vasodilators, NO had no major effect on gas exchange or systemic haemodynamics, while PGI2 and nifedipine both induced systemic hypotension (mean (SD) systemic arterial pressure 72 (14) versus 89 (19) mm Hg with PGI2 and 72 (15) versus 86 (17) mm Hg with nifedipine, p < 0.05) and hypoxaemia (PaO2 8.7 (1.4) versus 10.8 (1.0) kPa with PGI2 and 8.6 (1.4) versus 10.2 (1.5) kPa with nifedipine, p < 0.05) and increased venous admixture (28 (9) versus 14 (4)% with PGI2 and 22 (9) versus 13 (5)% with nifedipine, p < 0.05). CONCLUSIONS: NO inhalation can accurately predict a vasodilator response to nifedipine in patients with severe pulmonary hypertension without adverse effects on systemic haemodynamics and gas exchange. This absence of side effects may make it a more appropriate agent for testing the vasodilator response.

Relationship between pulmonary oxygen consumption, lung inflammation, and calculated venous admixture in patients with acute lung injury.

OBJECTIVE: To determine in patients with acute lung injury whether increased pulmonary oxygen consumption (VO2pulm), computed as the difference between oxygen consumption measured by indirect calorimetry (VO2meas) and calculated by the reverse Fick method (VO2Fick), would: (1) correlate with the degree of lung inflammation assessed by bronchoalveolar lavage (BAL); (2) lead to an overestimation of calculated venous admixture (Qva/Qt). DESIGN: Prospective study. SETTING: University hospital, medical intensive care unit. INTERVENTION: None. MEASUREMENTS AND RESULTS: In nine mechanically ventilated patients with acute lung injury (Apache II 12 +/- 5, lung injury score 2 +/- 0.6, mean +/- SD), whole-body VO2 (VO2wb) was determined simultaneously by indirect calorimetry and the reverse Fick technique, after which BAL was immediately performed. VO2meas was significantly higher than VO2Fick (128 +/- 24 and 102 +/- 18 ml/min per m2, respectively, p < 0.001). Median VO2pulm was 25.3 ml/min per m2 (range 1.98-51.5), thus representing 19 +/- 11% of VO2wb. Total BAL cellularity was increased in all patients (median 47, range 24-200 x 10(4)/ml), as was the total polymorphonuclear (PMN) count (median 78 range 5-93 x 10(4)/ml). Macrophage counts were in the normal range. There were raised BAL levels of interleukin-6 (IL-6) (median 945, range 23-1800 ng/ml) and elastase (median 391, range 5-949 ng/ml). Median protein levels were 270 micrograms/ml (range 50-505). There was no correlation between VO2pulm and BAL cellularity, PMNs, elastase, IL-6, or protein. Qva/Qt was 31.7 +/- 8%. Qva/Qt, corrected for the presence of VO2pulm, (Qva/Qtcorr), was 30.3 +/- 8% (P < 0.01 vs Qva/Qt), a 4.2% overestimation due to VO2plum. There was no correlation between Qva/Qt or Qva/Qtcorr and VO2pulm. CONCLUSIONS: In mechanically ventilated patients with acute lung injury, VO2pulm was increased and led to a 19% underestimation of VO2wb determined by the reverse Fick method, as well as to a 4.2% overestimation of calculated Qva/Qt. Lung inflammatory activity was increased, as assessed by BAL cellularity, IL-6 and elastase levels. However, there was no correlation between VO2pulm and the intensity of pulmonary inflammation.

Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome.

OBJECTIVE: To measure the effects of rapid permissive hypercapnia on hemodynamics and gas exchange in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: 18-bed, medical intensive care unit, university hospital. PATIENTS: 11 mechanically ventilated ARDS patients. INTERVENTION: Patients were sedated and ventilated in the controlled mode. Hypercapnia was induced over a 30-60 min period by decreasing tidal volume until pH decreased to 7.2 and/or P50 increased by 7.5 mmHg. Settings were then maintained for 2 h. RESULTS: Minute ventilation was reduced from 13.5 +/- 6.1 to 8.2 +/- 4.1 l/min (mean +/- SD), PaCO2 increased (40.3 +/- 6.6 to 59.3 +/- 7.2 mmHg), pH decreased (7.40 +/- 0.05 to 7.26 +/- 0.05), and P50 increased (26.3 +/- 2.02 to 31.1 +/- 2.2 mmHg) (p < 0.05). Systemic vascular resistance decreased (865 +/- 454 to 648 +/- 265 dyne.s.cm-5, and cardiac index (CI) increased (4 +/- 2.4 to 4.7 +/- 2.4 l/min/m2) (p < 0.05). Mean systemic arterial pressure was unchanged. Pulmonary vascular resistance was unmodified, and mean pulmonary artery pressure (MPAP) increased (29 +/- 5 to 32 +/- 6 mmHg, p < 0.05). PaO2 remained unchanged, while saturation decreased (93 +/- 3 to 90 +/- 3%, p < 0.05), requiring an increase in FIO2 from 0.56 to 0.64 in order to maintain an SaO2 > 90%. PvO2 increased (36.5 +/- 5.7 to 43.2 +/- 6.1 mmHg, p < 0.05), while saturation was unmodified. The arteriovenous O2 content difference was unaltered. Oxygen transport (DO2) increased (545 +/- 240 to 621 +/- 274 ml/min/m2, p < 0.05), while the O2 consumption and extraction ratio did not change significantly. Venous admixture (Qva/Qt) increased (26.3 +/- 12.3 to 32.8 +/- 13.2, p < 0.05). CONCLUSIONS: These data indicate that acute hypercapnia increases DO2 and O2 off-loading capacity in ARDS patients with normal plasma lactate, without increasing O2 extraction. Whether this would be beneficial in patients with elevated lactate levels, indicating tissue hypoxia, remains to be determined. Furthermore, even though hypercapnia was well tolerated, the increase in Qva/Qt, CI, and MPAP should prompt caution in patients with severe hypoxemia, as well as in those with depressed cardiac function and/or severe pulmonary hypertension.

The repeated measurement of vital capacity is a poor predictor of the need for mechanical ventilation in myasthenia gravis.

OBJECTIVE: Testing the hypothesis that, in myasthenia gravis (MG), repeated measurements of vital capacity (VC) and various parameters derived from this measurement [median or lowest value of measured VCs during hospitalization, VC values < 20 ml/kg body weight (BW) or < 13 ml/kg BW, or an index assessing the variability of VC values during the whole ICU stay] could predict the need for intubation and mechanical ventilation (MV), as has been shown in other neuromuscular diseases with respiratory failure. DESIGN: Retrospective study with medical chart revision of all the patients with MG and respiratory failure admitted to our intensive care unit between 1985 and 1993. SETTING: Medical intensive care unit (15 beds) of a university hospital. PATIENTS AND METHODS: Five patients suffering from ten episodes of acute respiratory failure due to their decompensated MG. Repeated measurements of arterial blood gases and VC by trained respiratory therapists, at least every 4 h. RESULTS: There was no difference in any of these parameters between patients eventually requiring MV (four episodes) and those in whom mechanical ventilation was not necessary (six episodes). CONCLUSIONS: VC repeated measurements is a poor predictor of the need for further MV in MG patients. This can probably be ascribed to the erratic nature of MG, a disease whose course is largely influenced by many parameters (infection, treatment modifications, initiation of corticosteroid therapy, stress, psychological factors, etc.). Early admissions to the ICU of MG patients with respiratory dysfunction is thus recommended.

[Cytokine inhibitors in intensive care]. / Les inhibiteurs des cytokines en réanimation.

OBJECTIVE: To examine three typical disease states seen in intensive care, sepsis, Fulminant purpura and acute respiratory distress syndrome (ARDS) to assess the implication of cytokines in their pathogenesis and particularly in the clinical applications of possible cytokine inhibitors. SOURCE OF DATA: The data bank of MedLine and the Index Medicus 1985-1993 and the first part of 1994. These sources have enabled us to consult publications in French and English and to include information on both animals and humans. The publications issued from Intensive Care Congresses have also been scrutinised; the Société de Réanimation de Langue Française, The American Thoracic Society and the 13th and 14th International Symposium on Intensive Care and Emergency Medicine, Brussels. SELECTION OF DATA: This review emphasizes certain areas of work including recognised work which has been published on the immunotherapy of sepsis in man, on those papers which have been published as a preliminary communication in the from of a summary and on certain papers relating to animal work which are regularly cited in Intensive Care literature. DISCUSSION: The relationship between cytokines and the three selected disease states have been briefly described. The greater part of those papers which have either been published or are in the process of being published present pharmacotherapeutic data in phase 2 or phase 3 in relationship to anticytokines and sepsis. As for the treatment of Fulminant purpura and ARDS, using anticytokine antibodies in 1994 we are still in the stage of hypothesis and speculation. CONCLUSIONS: Future clinical strategies designed to combat. Future clinical strategies designed to fight against the most critical diseases in intensive care medicine require some use of any kind of immunotherapy. In animal studies, convincing data are available showing that immunotherapy improves the prognosis of sepsis, whereas in humans, to date, the results appear to be deceiving. Future research in this direction is mandatory, in sepsis and in other disease states, like ARDS, because no other hope for treating these patients seems to appear in a near future.

Early hydrogen peroxide-induced pulmonary endothelial cell dysfunction: detection and prevention.

OBJECTIVES: To determine a) whether hydrogen peroxide-induced, early lung endothelial cell dysfunction can be detected in an isolated, perfused, rat lung model; and b) whether the organic phosphothioate N-(2-mercaptoethyl)-1,3-propanediamine, which protects cells in culture against hydrogen peroxide-mediated damage, can exert the same protection in this model. DESIGN: Intervention study; before-after trial. SETTING: Research laboratory. MODEL: Isolated, perfused, rat lung model. INTERVENTION: Continuous hydrogen peroxide infusion at increasing concentrations and infusion times, preceded or not by a N-(2-mercaptoethyl)-1,3-propanediamine infusion. MEASUREMENTS AND MAIN RESULTS: Early pulmonary endothelial cell alterations, assessed by the lung extraction (% extraction) of 123I-metaiodobenzylguanidine. Permeability edema by % extraction of 125I-human serum albumin and the lung dry-to-wet weight ratio. Control experiments: % extraction-123I-metaiodobenzylguanidine: 21.7 +/- 3.8% (n = 7). With increasing concentrations of hydrogen peroxide (0.025, 0.125, 0.5, and 2 mmol), % extraction-123I-metaiodobenzylguanidine was progressively depressed (n = 28, ANOVA, p < .05), significantly decreased from controls at 2 mmol (10.2 +/- 5.0%, n = 7, p < .05). When the 2-mmol hydrogen peroxide infusion was preceded by the N-(2-mercaptoethyl)-1,3-propanediamine (2 mmol) infusion, % extraction-123I-metaiodobenzylguanidine (19.9 +/- 2.9%, n = 5) was not significantly different from controls (n = 7) and was significantly greater than after the 2-mmol hydrogen peroxide infusion alone (8.7 +/- 7.4%, p < .05, n = 8). In all experiments, % extraction of human serum albumin ratio and dry-to-wet weight ratio were not significantly different from that of controls. CONCLUSIONS: a) Hydrogen peroxide-induced lung endothelial cell dysfunction was detected at an early stage, before any permeability defect appeared; b) N-(2-mercaptoethyl)-1,3-propanediamine protected against such damage.

Bronchoscopy in the intensive care unit.

The development of the flexible, fiberoptic bronchoscope has made bronchoscopic examinations possible in ICU patients undergoing mechanical ventilation. Over the years, the number of such procedures has greatly increased, with both diagnostic and therapeutic objectives, such as performing difficult intubation, management of atelectasis and hemoptysis, diagnosis of nosocomial pneumonia in ventilated patients, and early detection of airway lesions in selected situations, such as high-frequency ventilation. The complication rate can be kept low if the endoscopist has a precise knowledge of the many pathophysiological and technical facets particular to bronchoscopy under these difficult conditions. This article reviews some of these aspects, in the light of our personal experience.