[Role of radiotherapy in the management of non-Hodgkin lymphomas]. / Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens.

The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.

[Diagnostic value of the SHAPE questionnaire in recognition of the hyperventilation syndrome in children: a pilot study]. / Valeur diagnostique du questionnaire SHAPE pour le syndrome d'hyperventilation de l'enfant : étude pilote.

OBJECTIVE: Determination of a diagnostic scoring method for hyperventilation syndrome (HVS) in children and proposal of a simplified questionnaire. METHOD: We used the main clinical signs of HVS in children and adolescents identified in a previous study and classified them according to their odds ratios (OR). The intensity of each sign, measured using a visual analogic scale in the previous study, led us to analyze several scoring methods, with a breakdown between major and minor signs according to their OR. Building receiver operating characteristics (ROC) curves allowed us to choose the best diagnostic combination. RESULTS: A sample of 85 children and adolescents aged from 7 to 20 years (mean age, 11.9 years) was tested. This sample comprised 45 children with isolated HVS or HVS associated with asthma and 40 controls, with asthma but without HVS or attending our emergency unit after trauma. Seven respiratory signs and 10 nonrespiratory signs were selected. For each scoring method, a significant difference was observed between HVS and non-HVS patients. The most suitable area under the curve (0.934) and the best combination between specificity and sensitivity (Sp=0.90 and Se=0.82) were obtained when the scoring method was 0,3,6 for major signs, and 0,1,2 for minor signs, according to perceived intensity of each sign ("never or almost never", "sometimes" or "often or very often"). CONCLUSION: Since no gold standard is available to confirm the diagnosis of HVS in children, we propose using a simplified questionnaire composed of 17 items to compute a diagnostic score. The questionnaire will be validated shortly in a new prospective study.

[A diagnostic questionnaire for the hyperventilation syndrome in children]. / Elaboration d'un questionnaire diagnostique du syndrome d'hyperventilation chez l'enfant.

INTRODUCTION: Intensive efforts should be made to diagnose the hyperventilation syndrome (HVS) at an early stage as this will prevent stigmatisation and reinforcement of symptoms. It will also prevent children from undergoing unnecessary medical examinations and treatment. A diagnostic questionnaire should be useful for this purpose. METHODS: We administered a questionnaire with 16 respiratory symptoms and 23 non respiratory symptoms to 25 children with HVS alone, 20 with asthma and HVS, and two control groups: 20 children with asthma without HVS and 20 presenting with trauma. For each symptom a visual analogue scale (VAS) was completed. The symptoms for which the mean VAS values were significantly different between the children with HVS and the controls were subject to principal component analysis after varimax rotation with Kaiser normalisation. RESULTS: There was no significant difference in symptoms between HVS children with or without asthma. The five major respiratory symptoms were: throat-clearing, sniffing, difficulty in breathing in, sighing and yawning. The combined sensitivity of those symptoms was 99%, the combined specificity 24%. The five major non-respiratory symptoms were: anxiety, difficulty in going to sleep, general fatigue, abdominal pain, and joint pains. The combined sensitivity of those symptoms was 99%, the combined specificity 36%. CONCLUSIONS: We performed a simplified diagnostic questionnaire for HVS in healthy and asthmatic children and found 5 respiratory and 5 non-respiratory symptoms of significance.

[Metabolic acidosis after cardiac surgery with cardiopulmonary bypass revisited with the use of the Stewart acid-base approach]. / Evaluation de la théorie de Stewart lors de l'acidose métabolique survenant après chirurgie cardiaque sous circulation extracorporelle.

INTRODUCTION: According to the Stewart approach of acid-base regulation, chloride from either volume replacement or cardiopulmonary bypass (CPB) priming solution may induce metabolic acidosis. The alternative hypothesis stands in volume dilution with solutions free of bicarbonate. OBJECTIVES: Evaluate the acid-base status of patients undergoing cardiac surgery with CPB priming containing chloride and bicarbonate. MATERIAL AND METHODS: Prospective study. METHODS: Twenty-eight patients were prospectively included. Priming of CPB contained 47.4 mmol/l of bicarbonate and 97.7 mmol/l of chloride. Arterial blood samples were taken at 3 timings: prior (T1) and after (T2) CPB, and on arrival in the ICU (T3). Following measurements were performed: Na(+), K(+), Cl(-), Mg(++), Ca(++), phosphates, albumin, lactate and arterial blood gases. RESULTS: After CPB respiratory acidosis was observed. There was a significant increase of chloride with a decrease in apparent strong ion difference (SIDa). At the same time bicarbonate and base excess (BE) remained constant. A significant but weak correlation between BE and SIDa existed (r(2) = 0.06, p=0.024). On the contrary, no correlation was found between variations of BE and SIDa. However, the correlation was stronger between values and variations of bicarbonate and BE (respectively r(2)=0.605, p<0.0001 and r(2)=0.495, p<0.0001). CONCLUSION: No metabolic acidosis occurred after cardiac surgery when CPB was primed with bicarbonate. Therefore, it appears that chloride administration is not the main mechanism being involved in the acid-base regulation. This reinforces the hypothesis that metabolic acidosis during CPB may mainly be due to dilution of bicarbonate.

Cardiac output measurements in off-pump coronary surgery: comparison between NICO and the Swan-Ganz catheter.

BACKGROUND: The aim of this prospective study was to compare continuous cardiac output measurements of the non-invasive cardiac output system (NICO) with the pulmonary artery catheter during off-pump coronary bypass surgery. METHODS: Twenty-two patients enrolled for off-pump coronary surgery received both a pulmonary artery catheter and a non-invasive cardiac output system for measurement of cardiac output. Data were compared by the Bland-Altman method to calculate the degree of agreement and to analyse if a significant difference existed between the two methods of cardiac output measurements. RESULTS: Perioperatively, the non-invasive cardiac output underestimated cardiac output, but postoperatively overestimated it. The limits of agreement were larger during surgery compared to the postoperative period (-3.1; +2.5 vs. -1.4; +2.2 L min(-1)). Perioperatively, cardiac output measured with the pulmonary artery catheter varied from 0.5 to 7.5 L min(-1) (mean 3.6 L min(-1)) and with the non-invasive cardiac output from 0.5 to 8.4 L min(-1) (mean 3.9 L min(-1)). Postoperatively, these were 2.5-7.7 L min(-1) (mean 4.5 L min(-1)) and 2.3-8.4 L min(-1) (mean 4.9 L min(-1)), respectively. CONCLUSION: During off-pump cardiac surgery, the non-invasive cardiac output reliably measures cardiac output and does it more rapidly than a pulmonary artery catheter and may be more useful in order to detect rapid haemodynamic changes.

[Benchmark of a high-frequency jet ventilator, the Mistral]. / Etude d'un respirateur de jet ventilation, le Mistral, sur banc d'essai.

OBJECTIVE: To test a high-frequency jet ventilator, the Mistral (Acutronic Laboratory) on a lung model. METHODS: The jet ventilator Mistral was tested with two connectors (7 and 20 ml) and four catheters. Pressure and flow measurements were performed by varying the driving pressure (1 to 3 bars), the I/T ratio (0.25, 0.35, 0.45) and the frequency (1 to 5 Hz). Recorded data were: the volume delivered by the ventilator, the pressure measured in the connecting line between the ventilator and the injector and the difference between the end expiratory pressure measured by the ventilator through the injector and the tracheal pressure. RESULTS: An increase in driving pressure induced a proportional increase in minute volume whatever the injection catheter used. After insufflation, when a Seldicath catheter was used, the pressure decrease was the slowest and the time constant the longest. Increase in frequency or I/T ratio, particularly beyond 0.35, was associated with an increase of the end expiratory pressure measured by the respirator. The gradient of pressure measured by the respirator and by an external sensor was lower with the 7 ml connector whatever the catheter used, and was larger with the Seldicath catheter. CONCLUSION: The use of a low volume connector should be preferred, because it allows the measurement of the end expiratory pressure for a larger range of driving pressure, expiratory time and catheters. The performances of the Seldicath catheter are below those of the other catheters studied.

[Right atrial rupture after abdominal blunt trauma]. / Rupture de l'auricule droite après traumatisme fermé abdominal.

If the cardiac injuries are frequent after closed chest traumatism, the cardiac injuries after abdominal closed traumatism are unusual but serious. We report the case of a right auricular rupture associated with a liver injury after a closed abdominal traumatism. The diagnosis was suspected on the TDM and confirmed by echocardiography. An emergency sternotomy was performed due to sudden haemodynamic instability. The initial clinical signs are often misleading. However the diagnosis must be made quickly and the treatment begun without delay.

[Hyperventilation syndrome in children]. / Le syndrome d'hyperventilation pulmonaire chez l'enfant, revue de la litterature.

Hyperventilation syndrome is frequent in adults. There are only very few and very ancient publications in children. Diagnosis is sometimes difficult, because the symptoms often mimic those of organic diseases. Hyperventilation syndrome and organic diseases, especially asthma, often coincide. Intensive efforts should be made to diagnose hyperventilation syndrome at an early stage because this will prevent stigmatization and fixation of symptoms and disease, and also prevent children from undergoing unnecessary medical examinations and therapies. The authors review the literature about hyperventilation syndrome in children.

[Written asthma action plans: a useful tool for self-management]. / Le plan d'action écrit : un outil pour l'autogestion de l'asthme.

Written action plans for asthma have been recommended for many years. However, despite the fact that their effectiveness has been demonstrated, they are not used enough. The plans that we propose are serviceable and the method that we suggest makes them easy to use in the treatment of asthmatic children. These plans are made for patients who do not use a peak-flow meter (plans based on symptoms) and those who control this tool (plans based on peak expiratory flow).

[Prevention of venous thromboembolism following cardiac, vascular or thoracic surgery]. / Prévention de la maladie thromboembolique veineuse périopératoire en chirurgie cardiaque, vasculaire et thoracique.

In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target = 1.1-1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.

Is muscle relaxant necessary for cardiac surgery?

The need for continuous and complete paralysis during the entire cardiac surgery has not yet been investigated and is still controversial. In a series of 87 patients undergoing cardiac surgery with normothermic cardiopulmonary bypass, we studied the delay of recovery, incidence of residual paralysis, unwanted patient movement, and difficult surgical conditions after a single dose of atracurium (0.5 mg/kg) or cisatracurium (0.15 mg/kg). Anesthesia was induced with etomidate and remifentanil followed by tracheal intubation. The delay to obtain a train-of-four ratio of >0.9 was longer with cisatracurium than with atracurium (86 +/- 18 versus 97 +/- 19 min). However, at the end of surgery, this ratio was >0.9 for all patients. The presence of unwanted patient movement, diaphragmatic contractions, and difficult surgical conditions were observed. Delay of extubation of the trachea was similar in both groups. We conclude that there is no need for continuous neuromuscular blockade during cardiac surgery. A single dose of either atracurium or cisatracurium is sufficient to provide efficient paralysis from the start of induction leading to quicker recovery from paralysis in fast-track cardiac surgery.

[A notice for use for patients who benifit from an adrenaline pen. "Having an emergency kit is a good thing but knowing how to use it is better"]. / Une notice à l'usage du patient bénéficiant d'un stylo d'adrénaline. "Avoir une trousse d'urgence c'est bien, savoir l'utiliser en cas de besoin, c'est mieux".

We realized that it is essential that the patient who has an auto injector also has the direction sheet in its emergency bag. Patients, families but also young medical doctors' remarks and reflexions led us to create an explanatory didactic, precise, illustrated and practical direction sheet. The goals are to gather succinct information about the patient (personal contact information, medical history); remind emergency numbers (15 or 112) and the emergency treatment (antihistamine, broncholitor if necessary, epinephrine shots). It also indicates step by step how to use the auto injector (Anapen) and emphasizes the need for a medical supervision if the shot has been used. We present this direction sheet and the way to use it.

Relationship between phosphatidic acid level and regulation of protein transit in colonic epithelial cell line HT29-cl19A.

Colonic epithelial HT29-cl19A cells are polarized and secrete proteins among which alpha(1)-antitrypsin represents about 95%. Secretion occurs via a constitutive pathway, so that the rates of secretion directly reflect the rates of protein transit. In this paper we have demonstrated that: 1) in resting cells phospholipase D (PLD) is implicated in the control of apical protein transit; 2) phorbol esters stimulate apical protein transit (stimulation factor 2.2), which is correlated with a PLD-catalyzed production of phosphatidic acid (PA) (2.45-fold increase); 3) the stimulation of cholinergic receptors by carbachol results in an increase (stimulation factor 1.45) of apical protein transit which is independent of protein kinase C and PLD activities, but related to PA formation (1.7-fold increase) via phospholipase(s) C and diacylglycerol kinase activation; 4) an elevation of the cAMP level enhances apical protein transit by a PA-independent mechanism; 5) a trans-Golgi network or post-trans-Golgi network step of the transit is the target for the regulatory events. In conclusion, we have shown that PA can be produced by two independent signaling pathways; whatever the pathway followed, a close relationship between the amount of PA and the level of secretion was observed.

EGF precursor mRNA and membrane-associated EGF precursor protein in rat exorbital lacrimal gland.

This study was designed to demonstrate the presence of epidermal growth factor (EGF) in the rat exorbital lacrimal gland. EGF precursor gene transcription was demonstrated first by RT-PCR analysis of lacrimal gland RNA using a set of specific primers and second by Northern blot analysis of rat lacrimal gland mRNA. A rabbit polyclonal antibody (rEGF2) directed against rat submaxillary gland EGF was used to detect EGF-containing proteins by RIA. Results indicate that the rat lacrimal gland does not contain detectable soluble and mature EGF but that the EGF immunoreactivity is associated with the membrane-enriched fraction. Analysis of the detergent-solubilized membrane proteins by gel filtration shows that membrane-associated EGF immunoreactivity was present as a high-molecular-mass protein. Moreover, as shown by Western blot analysis, a specific anti-rat EGF precursor antibody (ppEGF1) can immunoprecipitate a 152-kDa EGF-containing protein. Taken together, these results demonstrate for the first time both EGF precursor gene transcription and EGF precursor protein expression in a lacrimal tissue, i.e., the rat exorbital lacrimal gland. The demonstration that EGF appears to be stored only as its full-length membrane precursor may provide important information to study the regulation of its secretory process.

A "septide-sensitive" receptor is not involved in tachykinin-mediated secretory and inositol phosphate responses in rat parotid gland: are several transduction pathways involved after the stimulation of the NK1 receptor?

In the rat parotid gland, the neuropeptide substance P (SP), as well as SP(4-11), and septide elicited inositol phosphate production (EC50 values 0.44, 2, and 20 nM, respectively). No additivity of the maximal response to the three agonists was observed. SP, SP(4-11), and septide also stimulated protein secretion; for SP, two EC50 were determined (0.5 and 160 nM), whereas a single one could be determined for SP(4-11) and septide (EC50 values 15 and 20 nM, respectively). The selective tachykinin NK1 receptor antagonist RP67580 acted as a competitive inhibitor of both SP- and SP(4-11)-induced inositol phosphate production. Its effect on septide-induced inositol phosphate production was noncompetitive. RP67580 is apparently as potent at antagonizing septide, SP, or SP(4-11) (in all cases KB = 3 nM). These results show that in parotid gland, only NK1 receptors are activated by SP, SP(4-11), and septide. We also showed that the protein secretion stimulated by SP was inhibited competitively by RP67580, whereas the effect of RP67580 was noncompetitive on protein secretion when SP(4-11) or septide was used. Our data indicate that in rat parotid gland, the existence of a specific "septide-sensitive" receptor can be ruled out and that only the NK1 receptor is present and mediates cellular responses. Taken together, these results show that in this tissue the NK1 receptor would present at least two different binding sites that could be coupled to different transduction pathways and that would regulate protein secretion.

PKA inhibitor, H-89, affects the intracellular transit of regulated secretory proteins in rat lacrimal glands.

We tested the effect of H-89, a protein kinase A (PKA) inhibitor, on the intracellular transit of the regulated secretory proteins in rat lacrimal glands. We show that H-89, by itself, induces the secretion of newly synthesized proteins trafficking in its presence but not of proteins already stored in the mature secretory granules. This secretion does not depend on the presence of extracellular Ca2+. The proteins released are identical to those secreted after cholinergic stimulation or under the action of the ionophore A-23187, but the secretion level is approximately 40% lower. The effect of H-89 seems to be due to PKA inhibition because other protein kinase inhibitors (calphostin C, chelerythrine, H-85) do not induce secretion. We further show that H-89 does not modify the rate of glycoprotein galactosylation but induces the secretion of newly galactosylated glycoproteins. Finally, we used a "20 degrees C block" procedure to show that H-89 affects a trans-Golgi network (TGN) or post-TGN step of the secretory pathway. Our results demonstrate that, in lacrimal cells, H-89 affects the intracellular trafficking of secretory proteins, suggesting a role for PKA in this process.

Detoxification mechanism in the rat extraorbital lacrimal gland: conjugation of brefeldin A to glutathione.

In this work the existence of a glutathione based detoxification system in rat lacrimal glands is reported. We showed that brefeldin A, a drug used as a tool for the study of intracellular trafficking mechanisms, was inactivated by metabolization and converted into two derivatives. We purified them by high performance liquid chromatography and determined, by mass spectroscopy, that they correspond to glutathione and cysteine derivatives of BFA. The determination of the respective amounts of these derivatives in the medium and the tissue in different experimental conditions, revealed that glutathione-BFA is formed in the tissue, excreted from the cells, cleaved by gamma-glutamyl transpeptidase and finally converted to cysteine-BFA.