DypB peroxidase for aflatoxin removal: New insights into the toxin degradation process.

Aflatoxin B1 (AFB1) is one of the most potent carcinogens and a widespread food and feed contaminant. As for other toxins, many efforts are devoted to find efficient and environmentally-friendly methods to degrade AFB1, such as enzymatic treatments, thus improving the safety of food and feed products. In this regard, the dye decolorizing peroxidase of type B (DypB) can efficiently degrade AFB1. The molecular mechanism, which is required to drive protein optimization in view of the usage of DypB as a mycotoxin reduction agent in large scale application, is unknown. Here, we focused on the role of four DypB residues in the degradation of AFB1 by alanine-scanning (residues 156, 215, 239 and 246), which were identified from biochemical assays to be kinetically relevant for the degradation. As a result of DypB degradation, AFB1 is converted into four products. Interestingly, the relative abundancy of these products depends on the replaced residues. Molecular dynamics simulations were used to investigate the role of these residues in the binding step between protein and manganese, a metal ion which is expected to be involved in the degradation process. We found that the size of the haem pocket as well as conformational changes in the protein structure could play a role in determining the kinetics of AFB1 removal and, consequently, guide the process towards specific degradation products.

[The role of electromagnetic navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions]. / Place de la navigation électromagnétique endobronchique pour le diagnostic de lésions pulmonaires périphériques.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a recent, minimally invasive procedure utilized to guide endoscopic diagnostic tools to peripheral pulmonary nodules. The place of this technology among other diagnostic procedures remains uncertain. METHOD: We analyzed our 30 first months of ENB used in the diagnosis of 106 lesions in 101 patients, from June 2016 to December 2018. Follow-up and final diagnosis was completed for 95 lesions (90%). RESULTS: ENB was performed for 3.5% of all patients referred for abnormal findings on pulmonary imaging, and represented 19% of second line procedures for peripheral pulmonary lesions. Procedures were performed under general anesthesia, with a mean duration of 35min. The sensitivity of ENB was 64% (95%CI: 52-74%) for lesions with a mean diameter of 21mm, with an improvement over time (sensitivity 69% in the last 18 months). The presence of a bronchus within the lesion (bronchus sign) was associated with an increased sensitivity of 74%. Pneumothorax occurred in 5 patients (5%) of which 4 required drainage. There was no hemoptysis, and no death related to the procedure. CONCLUSION: ENB is a minimally invasive procedure reaching acceptable sensitivity in the most difficult patients. ENB can be recommended for the diagnosis of peripheral pulmonary nodules when no other procedure is successful or possible. Its use as a first choice procedure is, for the moment, limited by the cost, but must be weighed against that of non-diagnostic procedures, and the cost of complications of trans-thoracic lung biopsies.

[Endobronchial ultrasonography (EBUS) for the internist]. / Écho-endoscopie bronchique (EBUS) pour l'interniste.

Endobronchial ultrasonography (EBUS) is a recent mini-invasive technique allowing transbronchial needle aspiration (TBNA) of mediastinal lymph nodes as well as peribronchial lesions. EBUS was initially developed for lung cancer mediastinal staging. Over the years, indications for EBUS have been progressively extended to the scope of inflammatory disorders, mediastinal lymphomas, and infectious diseases. Particularly in immunosuppressed patients, including HIV-infected patients, EBUS allows the diagnosis of several diseases that involve the mediastinum, avoiding invasive surgical explorations such as mediastinoscopy or thoracoscopy. This review aims at discussing the technical aspects, and specifies indications, results, and limits of EBUS for the internist.

Structural analysis of protein Z gene variants in patients with foetal losses.

The role of protein Z (PZ) in the etiology of human disorders is unclear. A number of PZ gene variants, sporadic or polymorphic and found exclusively in the serine protease domain, have been observed. Crystal structures of PZ in complex with the PZ-dependent inhibitor (PZI) have been recently obtained. The aim of this study was a structural investigation of the serine protease PZ domain, aiming at finding common traits across disease-linked mutations. We performed 10-20 ns molecular dynamics for each of the observed PZ mutants to investigate their structure in aqueous solution. Simulation data were processed by novel tools to analyse the residue-by-residue backbone flexibility. Results showed that sporadic mutations are associated with anomalous flexibility of residues belonging to specific regions. Among them, the most important is a loop region which is in contact with the longest helix of PZI. Other regions have been identified, which hold anomalous flexibility associated with potentially protective gene variants. In conclusion, a possible interpretation of effects associated with observed gene variants is provided. The exploration of PZ/PZI interactions seems essential in explaining these effects.

[Spontaneous regression of epithelial thymic tumours]. / Tumeurs épithéliales thymiques de régression spontanée.

INTRODUCTION: Spontaneous regression of an epithelial thymic tumour has been reported but seems extremely rare. Its mechanism is unknown. CASE REPORT: We report two cases of epithelial thymic tumour, either histologically proven or highly suspected on imaging, that regressed spontaneously (partially in one patient and totally in the other). CONCLUSION: Spontaneous regression of an epithelial thymic tumour is very rare but this possibility could lead to clinical and radiological monitoring rather than surgery in selected patients.

Fully endoscopic major pulmonary resection for stage I bronchial carcinoma: initial results.

INTRODUCTION: Several case-series studies of major pulmonary resection (MPR) by video-assisted thoracic surgery (VATS) for non-small-cell lung cancer (NSCLC) have been published, but fully endoscopic MPR is still very rarely performed. Our objective here was to report the outcomes in 71 patients recently managed using fully endoscopic MPR for NSCLC. METHODS: From 2007 to 2009, 635 patients with NSCLC underwent MPR (pneumonectomy, lobectomy or segmentectomy). Among them, 71 (11%) had features strongly suggesting clinical stage I NSCLC and were managed by fully endoscopic MPR, with no utility incision. Lobectomy was performed in 63 patients and segmentectomy in eight patients. Conversion to thoracotomy was required in two (2.8%) patients, because of a fused fissure in one and tight pleural adhesions in the other. Radical lymphadenectomy was performed in all patients. RESULTS: Of the 69 patients managed endoscopically, none died and none experienced intraoperative complications. Mean operating time was 226±38 minutes (range, 137-307 minutes) and mean intraoperative blood loss was 111±93mL (range, 0-450mL). The final histological examination showed stage I NSCLC in 52 patients, NSCLC with node involvement in nine patients (pN1 in 6 and pN2 in 3) and other types of malignancies in eight patients. Mean number of nodes removed was 21±8 after right-sided lymphadenectomy and 23±8 after left-sided lymphadenectomy and the mean number of dissected node sites was 3 (range, 2-5). The postoperative morbidity rate was 23%. Mean postoperative hospital stay length was 6.9±2 days (range, 3-12). CONCLUSION: Fully endoscopic MPR is safe and meets the criteria for oncological surgery.

[Totally endoscopic major pulmonary resection for stage I bronchial carcinoma: initial results]. / Résections pulmonaires majeures par voie totalement endoscopique pour carcinome bronchique de stade I: résultats initiaux.

INTRODUCTION: Several series of video-assisted (VATS) major pulmonary resection (MPR) for non small cell bronchial carcinoma (NSCBC) have been published recently. However, totally endoscopic MPR is still very uncommon. We report the initial results of a recent series of 71 patients. METHODS: From 2007 to 2009, 635 patients had a major pulmonary resection (pneumonectomy, lobectomy or segmentectomy) for NSCBC. Seventy-one out of these patients (11%) in whom a clinical stage I NSCBC was strongly suspected were operated on via a totally endoscopic approach, without mini-thoracotomy or utility incision. Sixty-three had a lobectomy and 8 a segmentectomy. There were 2 conversions to thoracotomy (2.8%), for a fused fissure (1 patient) and for tight pleural adhesions (1 patient). The resection was completed by a radical lymphadenectomy in all patients. RESULTS: For the 69 patients who had a totally endoscopic procedure, there was no mortality. No intraoperative complications occurred. The mean duration of operation was 226 minutes + or - 38 (range: 137-307 minutes). The mean intraoperative blood loss was 111 cc + or - 93 (range: 0-450 cc). Final pathological examination confirmed stage I NSCBC in 52 patients while 9 NSCBC were upstaged pN1 (n = 6) or pN2 (n = 3). In 8 cases, another type of malignant tumour was found. The mean number of lymph nodes collected was 21 + or - 8 after right-side lymphadenectomy and 23 + or - 8 after left-side lymphadenectomy and the mean number of dissected lymph node stations was 3 (range:2-5). Postoperative morbidity was 23%. The mean postoperative stay was 6.9 days + or - 2 (range: 3-12 days). CONCLUSIONS: MPR via a totally endoscopic approach is safe and fulfils the criteria for an oncological resection.

The NER proteins are differentially expressed in ever smokers and in never smokers with lung adenocarcinoma.

BACKGROUND: The expression levels of excision repair cross-complementation group 1 (ERCC1), replication protein A (RPA) and xeroderma pigmentosum group F (XPF) nucleotide excision repair proteins may be important in the response to platin-based therapy in lung cancer patients. It is not known whether ERCC1, RPA and XPF expression levels differ between ever smokers (ES) and never smokers (NS). PATIENTS AND METHODS: ERCC1, RPA and XPF expression levels were immunohistochemically evaluated in 125 patients with resected lung adenocarcinoma (AC) and carefully reviewed smoking status. RESULTS: ERCC1 was correlated with XPF (P = 0.001), but not with RPA (P = 0.11). In the univariate analysis, ERCC1 and XPF levels were higher in NS compared with ES (P = 0.004 and P = 0.003, respectively). In the multivariate analysis, the smoking status was predictive of the ERCC1 level [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.03-6.2] after adjustment for variables linked to the smoking status, including age and the presence of bronchioloalveolar (BAC) features. The smoking status was also predictive of both RPA (OR 6.7, 95% CI 1.5-33.3) and XPF levels (OR 12.5, 95% CI 2.9-50) after adjusting for age, sex and BAC features. CONCLUSION: In patients with resected lung AC, ERCC1, RPA and XPF expression levels are higher in NS compared with ES.

[Full thoracoscopic lobectomy and segmentectomy for benign or metastatic conditions]. / Lobectomies et segmentectomies par thoracoscopie exclusive pour pathologie bénigne ou métastatique.

INTRODUCTION: Several techniques for video-assisted pulmonary lobectomy have been reported. However full thoracoscopic lobectomy, i.e., without the help of a utility incision has seldom been performed. We report our results based on a series of resections for benign or metastatic conditions where mediastinal lymphadenectomy is not indicated. PATIENTS AND METHODS: Fifty-six patients (29 males and 27 females) with a mean age of 46 years (range: 8-82 years) had an attempted major pulmonary resection (54 lobectomies and 2 segmentectomies) via thoracoscopy alone for either a benign lesion (30 cases) or a metastasis (26 cases). RESULTS: There was no operative mortality. Six patients required conversion to thoracotomy (11%). In the 50 remaining patients who underwent an exclusively thoracoscopic operation, there was 1 intra-operative complication that was managed thoracoscopically. The duration of the procedure ranged from 65 to 230 minutes (mean: 157 minutes). Intra-operative blood loss was 55 cc (range: 0 to 200 cc) in the "metastasis group" and 109 cc (range: 0 to 280 cc) in the "benign lesion group". There were 5 postoperative complications (10%). Postoperative duration of stay ranged from 3 to 15 days (Mean: 6.7 days). All patients were seen at the first postoperative month and no clinical or radiological complication was noticed. CONCLUSION: Full thoracoscopic lobectomies are feasible and safe provided appropriate equipment is used and the surgical team is experienced in endoscopic surgery.

[Pleural diffusion of amoxicillin 1 and vancomycin in patients treated for post-surgical empyema]. / Empyème après chirurgie d'exérèse pulmonaire: étude de la diffusion pleurale de l'amoxicilline et de la vancomycine.

INTRODUCTION: Treatment of post surgical thoracic empyema consists of chest tube drainage, antibiotic administration, and in some cases surgical lavage of infected spaces. Data in human on the diffusion of antibiotics in pleural cavity after post surgical empyema are lacking. METHODS: We studied on 9 patients with post surgical thoracic empyema (including 6 pneumonectomy) the diffusion of 2 antibiotics commonly used in this situation: amoxicillin (for 7 patients) and vancomycin (for 2 patients). Antibiotics concentrations were measured after at least 3 days of treatment (3-12 days), in order to reach a plateau concentration in the pleural space. RESULTS: The ratio pleural/plasma antibiotic concentration was 1.96 (range: 0.6-4.9). The pleural infection was cured for 8 on 9 patients. The last patients required thoracostomy, and the outcome was favorable after this procedure. CONCLUSION: That the penetration of amoxicillin and vancomycin in pleural space after post surgical empyema is good. Pleural antibiotics concentrations are in the majority of cases higher than plasmatic concentrations.

Thoracoscopic palliative treatment of malignant pleural effusions: results in 273 patients.

BACKGROUND: The aim of this study was to analyze the results of pleurodesis for malignant pleural effusion performed by surgeons. PATIENTS AND METHODS: A series of 273 patients with malignant pleural effusion underwent thoracoscopy with the aim of performing a palliative pleurodesis. There were 94 males (34.4%) and 175 females (64.1%), ranging in age from 15 to 94 years (mean age: 60.6 years). The effusion was on the right side in 136 patients (49.8%), on the left side in 110 (40.3%), and bilateral in 27 (9.9%). Thoracoscopy was performed under general anaesthesia in all patients. Pleural biopsy was performed in two thirds of the patients (70.7%). Pleurodesis was produced by instillation of 5g of sterile asbestos-free talc; the chest tube was left in place a minimum of 3 days. It was removed when fluid drainage was less than 200 ml/24 h. Patients were usually discharged the day after chest tube removal. RESULTS: There was no intraoperative mortality. Two patients (0.7%) had intraoperative complications; 17 (6.2%) underwent a bilateral pleurodesis, and 10 (3.7%) had a pericardiopleural window. In 32 patients (11.7%) no pleurodesis was done, either because the lung did not properly re-expand (5.2%), or because of suspected infection, e.g., false membranes (1.9%), or because of multiple adhesions (4.6%). Finally, only 241 patients (88.3%) had a talc poudrage at the time of thoracoscopy. Duration of postoperative pleural drainage ranged between 1 and 11 days (mean: 3.64 days). The postoperative hospital stay ranged from 2 to 21 days (mean: 7.1 days). Pleural empyema occurred in 4 patients (1.5%) and was lethal in one patient. The mean follow-up period was 8.39 (7.2 months, and 172 patients had regular follow up. In this group, there were 24 recurrences (14%), 12 of which were treated by repeat pleurodesis. The results were very good in 133 patients (77.3%), acceptable in 35 patients (20.3%), and there was a failure in 4 patients (2.4%). CONCLUSIONS: Results of surgical thoracoscopy for malignant pleural effusion are good, with low morbidity. However, in debilitated patients, bedside talc slurry may be preferable.

Results of thoracoscopic pleural abrasion for primary spontaneous pneumothorax.

BACKGROUND: Several video-assisted techniques have been used to treat primary spontaneous pneumothorax (PSP). The aim of this study was to evaluate the results of thoracoscopic pleural abrasion for PSP. METHODS: From 1991 to 2003, 185 consecutive patients, 143 male and 42 female, aged 15 to 60 years (average 31.6) underwent thoracoscopic pleural abrasion for PSP. The indications for surgery were as follows: a first episode with persistent air leak in 33 patients (17.9%), a recurrent ipsilateral pneumothorax in 122 patients (65.9%), a previous contralateral pneumothorax in 23 patients (12.4%), and recurrence after surgical treatment in seven patients (3.8%). Bullae were resected in 163 patients (88.1%). Mechanical pleural abrasion was performed in all cases. RESULTS: There were no deaths. Intraoperative hemorrhage occurred in three patients. It was controlled via thoracotomy in one patient and via thoracoscopy in two patients. The postoperative complication rate was 8.1% (15/185). Complications included prolonged air leak in eight patients (4.3%), pleural effusion in two (1.1%), extrapleural hematoma in one (0.5%), chest wall infection in one (0.5%), atelectasis in one (0.5%), and hemorrhage in two (1.1%). Postoperative hospital stay ranged between 2 and 17 days (mean, 5). Mean duration of drainage was 3.8 days (range; 1-16). Postoperatively, 111 patients were contacted, with a mean follow-up of 36.5 months. Four of them had a recurrence (3.6%) that did not require reoperation. CONCLUSION: Thoracoscopic pleural abrasion associated with bullae resection is a safe and efficient treatment for PSP. Results remain stable in the long term.

[Acute respiratory failure due to Gemcitabine-induced pulmonary toxicity]. / Pneumopathie d'hypersensibilité à la Gemcitabine s'accompagnant d'insuffisance respiratoire aiguë

Gemcitabine is a therapeutic agent that has been recently employed in the treatment of various cancers. Pulmonary toxicity has rarely been described. We report a case of a patient treated with Gemcitabine who developed acute respiratory symptoms related to a hypersensitivity pneumonia. Despite a severe clinical and radiological presentation, the outcome was favorable with corticosteroid treatment. In the event of respiratory symptoms in patients receiving Gemcitabine further investigations (chest X-ray, thorax CT-scan, bronchoalveolar lavage) are indicated. In view of the severity of pulmonary toxicity that can be caused by Gemcitabine, re-introduction of treatment is not recommended. We compare our case with other published cases of Gemcitabine-induced pulmonary toxicity.

Early complications of thoracic endoscopic sympathectomy: a prospective study of 940 procedures.

BACKGROUND: Thoracic endoscopic sympathectomy (TES) has become the surgical technique of choice for treating intractable palmar hyperhidrosis and is usually considered as a simple and safe procedure. To evaluate the complication rate of TES, we conducted a prospective study of peri- and postoperative complications. METHODS: From 1995 to 1999, 467 consecutive patients were operated on for upper limb hyperhidrosis. There were 164 men and 303 women, ranging in age from 15 to 59 years (mean 31 years). In all but 5 cases, the procedure was bilateral. Eleven patients underwent a reoperation for failure; thus the total number of sympathectomies was 940. The procedure was performed in two stages in 182 patients and in one stage in 267 patients. All patients were seen 1 month after the operation. RESULTS: There was no mortality. The mean postoperative hospital stay was 2.3 days in the group of patients who were operated on in two stages and 1.1 day in patients who were operated on in one stage. There were three major complications: one tear of the right subclavian artery and two chylothoraces. There were 25 cases (5.3%) of bleeding (300 to 600 mL) during dissection of the sympathetic trunk due to injury to an intercostal vein; in all cases it was controlled thoracoscopically. There were 12 pneumothoraces (1.3%) after removal of chest tubes. All of these were unilateral. Four required chest drainage for a period of less than 24 hours. One patient had a mild pleural effusion. Four patients had a unilateral partial Horner Syndrome (0.4%) that disappeared within 3 months in 2 patients. The other 2 patients were lost to follow-up. One patient complained of rhinitis. CONCLUSIONS: Although morbidity was low, significant complications of TES occurred. Patients should be clearly warned that TES is not as minor a procedure as usually asserted. Complications as well as adverse effects should be considered when discussing this surgical indication.

[Mediastioscopic management of pleuropericardial cysts]. / Abord des kystes pleuro-péricardiques par médiastinoscopie.

We report two cases of paratracheal cystic tumors where no preoperative diagnosis could be established. Mediastinoscopy provided the diagnosis of pleuropericardial cyst. The mediastinoscopic approach allowed partial removal in one case and complete removal in the other.

Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma.

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

[Primary biphasic synovial sarcoma of the pleura]. / Synovialosarcome biphasique primitif de la plèvre.

A 36-year-old man presented with a pleural tumor. The first pathologic analysis diagnosed biphasic pleural malignant mesothelioma. However, the atypical clinical course, the early development of lung metastases and a new reading of histologic documents led to the diagnosis of primary pleural synovial sarcoma. The literature review is limited, as only nine other cases have been reported to date. Chest pain is the only constant clinical feature. Misleading interpretation of histologic material is frequent (6 of 10 cases). Only a complete immuno-histochemical study confronted with the clinical course can lead to the correct diagnosis. Because the efficacy of chemotherapy and/or radiotherapy is poor, surgery remains the basis of treatment, whenever possible. Evolution is mainly intra-thoracic, with multiple local recurrences and lung metastases. Prognostic is poor, a survival rate is similar to that of primary pulmonary sarcomas.

Curative irradiation of limited endobronchial carcinomas with high-dose rate brachytherapy. Results of a pilot study.

OBJECTIVES OF THE STUDY: Pilot study to assess high-dose rate (HDR) brachytherapy as sole treatment for limited endobronchial non-small cell lung carcinomas. INCLUSION CRITERIA: Proximal non-small cell lung cancer in a not previously irradiated area, with a maximal diameter of 1 cm, no visible tumor on CT scan, lack of other treatment options in patients with severe, chronic respiratory failure, surgery, or external radiotherapy for a previous lung cancer. TREATMENT PROTOCOL: Treatment was based on an escalating dose protocol. Patients received three to five fractions of 7 Gy prescribed at 10 mm from the center of the applicator, once a week. RESULTS: Nineteen patients were included in this trial. The first two patients received three fractions of 7 Gy, the four next patients received four fractions, and the 13 remaining patients were treated with five fractions of 7 Gy. Two months after the end of the procedure, tumors in 15 of 18 evaluable patients (83%) were locally controlled with negative results of biopsies. At 1 year, local control was still obtained in 12 of 16 evaluable patients (75%). With a mean follow-up of 28-months, 1-year and 2-year actuarial survival rates were 78% and 58%, respectively, with a 28-month median survival. One patient with local control died from hemoptysis 12 months after treatment. Two patients suffered from severe necrosis of the bronchial wall; one of them died from hemoptysis. CONCLUSIONS: HDR brachytherapy is an effective treatment for small endobronchial tumors. Late toxicity on the bronchial wall is still too high and was attributed mainly to contact between the catheter and the bronchial mucosa. Exclusive HDR brachytherapy should be restricted to carefully selected patients for whom there is no alternative curative treatment. New bronchial applicators and a lower dose per fraction may reduce the incidence and attenuate the severity of late complications.

[Acute pleurisy secondary to ovarian hyperstimulation after in vitro fertilization]. / Pleurésie aiguë secondaire à une hyperstimulation ovarienne après fécondation in vitro.

Pleurisies due to the syndrome of ovarian hyperstimulation typically accompany ascites and in their most severe form are associated with haemoconcentration, hypovolaemia and thromboembolic phenomena. It is not unusual in this context for pleural effusions to be isolated. They may occur during treatment for sterility by inducing ovulation, they are exudates and predominantly right sided. The pathophysiology is not clear and results in vascular hyperpermeability. Currently, no treatment aimed at the aetiology has proven its own efficacy. Spontaneous regression of the effusion is the rule but in severe forms, where the prognosis is uncertain, correction of hypovolaemia is a priority.