Severe pulmonary arterial hypertension and massive ascites in a patient with systemic lupus erythematosus and secondary Sjogren's syndrome.

BACKGROUND: Pulmonary arterial hypertension (PAH), is a rare manifestation of systemic lupus erythematosus (SLE), characterized by pulmonary arterial remodeling leading to right ventricular failure and death. To date, optimal management of SLE-associated PAH should be clarified, especially regarding the respective places of immunosuppressants and PAH vasodilator treatments. CASE REPORT: We report the case of a 48-year-old woman with SLE and secondary Sjogren syndrome, associated with severe PAH and lupus peritonitis with massive ascites, who showed a remarkable response, both for SLE flare and PAH, to a treatment combining immunosuppressants and pulmonary arterial vasodilator treatment. CONCLUSION: This observation highlights the interest of combining immunosuppressive therapy in SLE-PAH, whose modalities in association with PAH treatments should be clarified.

Cardiac mitochondrial oxidative capacity is partly preserved after cryopreservation with dimethyl sulfoxide.

BACKGROUND: Cardiac muscle cryopreservation is a challenge for both diagnostic procedure requiring viable tissues and therapeutic advance in regenerative medicine. Mitochondria are targets of both direct and indirect damages, secondary to congelation per se and/or to cryoprotectant's toxic effects, which participate to diminution of viability and/or functioning of cells after freezing. At the cardiac muscle level, only one study had investigated mitochondrial respiration after cryopreservation. OBJECTIVE: To determine the effect of cryopreservation on mitochondrial respiration of cardiac muscle. MATERIALS AND TMETHODS: We recorded mitochondrial respiration through complexes I, II, III and IV along with mitochondrial coupling in fresh and cryopreserved rat left ventricles samples and assessed difference of the means, correlation and agreement between the measures in all samples. RESULTS: Mitochondrial respiration was partly maintained up to 70% in cryopreserved samples whatever the substrate. A significant correlation was observed between fresh and cryopreserved samples (r = 0.71, p < 0.0001). However, mitochondrial coupling significantly decreased after cryopreservation (- 1.44 ± 0.15; p < 0.005) suggesting that mitochondrial intactness was not totally preserved by cryopreservation. Further, the fluctuations around the mean difference were wide (-14.06, +5.08 µmol/min/g), increasing with respiration rates (p < 0.0001). CONCLUSION: Thus, fresh samples extemporaneous analysis should be preferred when available despite the fact that cryopreservation using DMSO partly protect cardiac mitochondrial respiration and coupling. These data support the interest to further refine cryopreservation methods.

Effect of postconditioning on mitochondrial dysfunction in experimental aortic cross-clamping.

BACKGROUND: Cross-clamping of the aorta during abdominal aortic aneurysm surgery induces muscle ischaemia with resultant morbidity. This study tested whether ischaemic postconditioning would decrease mitochondrial dysfunction in skeletal muscle by reducing oxidative stress. METHODS: Three groups (9 rats each) underwent surgery, including a control group without ischaemia and an ischaemia-reperfusion group that had 3 h ischaemia induced by aortic clamping and collateral vessel ligation, followed by 2 h of reperfusion. The third group had ischaemia for 3 h then underwent postconditioning comprising three short intervals of ischaemia-reperfusion at the onset of reperfusion. Activity of complexes I, II, III and IV of the mitochondrial respiratory chain was monitored in gastrocnemius muscle, along with oxidative stress measured by dihydroethidium (DHE) staining and antioxidant defence determined by measurement of glutathione levels. RESULTS: Ischaemia-reperfusion alone caused a significant reduction in maximal oxidative capacity (-31.8 per cent; P = 0.002), activity of complexes II, III and IV (-34.5 per cent; P = 0.007) and complex IV activity (-30.6 per cent; P = 0.039). It also increased reactive oxygen species (DHE staining increased to 223.1 per cent of control value; P = 0.027) and reduced antioxidant defence (glutathione level -28.6 per cent; P = 0.039). Postconditioning counteracted these deleterious effects by increasing mitochondrial complex I, II, III and IV activities, restoring muscle DHE staining and preserving glutathione content. CONCLUSION: Ischaemic postconditioning protects skeletal muscle mitochondria against ischaemia-reperfusion injury by reducing oxidative stress and preserving antioxidant defence in an experimental model. Mitochondrial protection to reduce reperfusion injury in clinical vascular surgery may be warranted.

[Variation in ventilatory response to CO2 in patients treated by non-invasive ventilation]. / Variation de la réponse ventilatoire au CO2 chez des patients appareillés par ventilation non invasive.

INTRODUCTION: There are many mechanisms for improving the clinical and blood gas status of patients with the obesity hypoventilation syndrome (OHS) or chronic obstructive pulmonary disease (COPD) by non-invasive ventilation (NIV) at home. Our objective was to set up a pilot study to evaluate the potential modification of the sensitivity of the respiratory centers to CO2 by NIV in paired new COPD and OHS patients. METHODS: We assessed the sensitivity of the respiratory centers to CO2 by the Read method in 3 COPD patients and 3 OHS patients newly treated by NIV and again 3 months later. We compared their results to those of 6 control subjects. RESULTS: All the patients included had altered ventilatory responses to CO2 with slopes of less of than 1 L.min-1.mmHg-1. Mean coefficients of variation were significantly higher in patients than in healthy subjects (P=0.007). Patients who improved their CO2 sensitivity slope were those most observant of NIV. CONCLUSION: This work showed significant changes in the ventilatory response to hypercapnia in patients with either OHS or COPD after NIV therapy. The significance of these changes deserves to be studied.

Diffusing capacity of the lung for CO and pulmonary blood flow during incremental and intermittent exercise.

The aims of this study were to evaluate the feasibility of successive diffusing capacity of the lung for carbon monoxide (DLCO) measurements during two different exercise tests (upright cycling), and to compare the relationships between DLCO and pulmonary blood flow (Qc). Eight healthy subjects performed an incremental test (1-min step) and a strenuous 30-min intermittent-work exercise test (4 min at low and 2 min at high workload). Intrabreath DLCO and Qc were calculated by assessing the uptake of CO and C2H2 during exhalation. DLCO could be measured reliably up to 73-90% of peak oxygen consumption (VO2) during the incremental test, and up to 85-95% of peak VO2 during the intermittent test. The coefficients of variation of DLCO and Qc measured during two successive constant-load exercise tests were 5-6% and 7-11%, respectively. The highest values of DLCO, Qc and VO2 measured during the incremental and intermittent tests were similar (56 and 51 mL/mmHg/min for DLCO, 18.7 and 18.3 L/min, for Qc and 2.4 and 2.3 L/min for VO2, respectively). The main observed result was that the linear relationships between DLCO and Qc were similar whatever the exercise type. This allows DLCO comparisons, with regards to Qc, during different exercise protocols.

[Approaches to the pre-operative functional assessment of patients with lung cancer and preoperative rehabilitation]. / Bilan fonctionnel préopératoire du cancer bronchique et réhabilitation préopératoire.

Surgery is the best treatment for early lung cancer but requires a preoperative functional evaluation to identify patients who may be at a high risk of complications or death. Guideline algorithms include a cardiological evaluation, a cardiopulmonary assessment to calculate the predicted residual lung function, and identify patients needing exercise testing to complete the evaluation. According to most expert opinion, exercise tests have a very high predictive value of complications. However, since the publication of these guidelines, minimally-invasive surgery, sublobar resections, prehabilitation and enhanced recovery after surgery (ERAS) programmes have been developed. Implementation of these techniques and programs is associated with a decrease in postoperative mortality and complications. In addition, the current guidelines and the cut-off values they identified are based on early series of patients, and are designed to select patients before major lung resection (lobectomy-pneumonectomy) performed by thoracotomy. Therefore, after a review of the current guidelines and a brief update on prehabilitation (smoking cessation, exercise training and nutritional aspects), we will discuss the need to redefine functional criteria to select patients who will benefit from lung surgery.

[Physiological functional tests to evaluate pulmonary arterial hypertension]. / Explorations fonctionnelles dans l'hypertension artérielle pulmonaire.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare and complex disease, which requires careful diagnostic evaluation. STATE OF THE ART: Most patients have a mild decrease in lung volumes and a moderate decrease in carbon monoxide transfer factor. Mild to moderate arterial hypoxaemia, is often present, associated with a mild respiratory alkalosis. When hypoxaemia is severe, it may represent an intracardiac shunt. Right heart catheterisation is required to confirm the diagnosis and in most cases shows a significant elevation of pulmonary artery pressure due to an increase in pulmonary vascular resistance. The haemodynamic profile and the response to an acute pulmonary vasodilator challenge are determinants of prognosis. Finally, exercise capacity which is usually assessed by the six minute walk test provides an overall functional measure of disease severity, response to therapy, and progression. PERSPECTIVES: Functional evaluation of the heart using echocardiography will play an increasing role in the evaluation of PAH. CONCLUSIONS: Physiological measurements in PAH have several objectives. They form part of the diagnostic definition, allow the exclusion of other conditions and are tools for the assessment of severity, prognosis and response to therapy.

Severe colchicine intoxication in a renal transplant recipient on cyclosporine.

Using colchicine to treat an acute gout crisis in an organ transplant recipient (TR) on cyclosporine (CsA) may result in life-threatening intoxication. We report the case of a 59-year-old kidney transplant recipient on CsA who was treated with colchicine for acute gout crisis. Seven days later, he developed rhabdomyolysis with progressive quadriparesis, hematologic toxicity and acute renal failure. CsA inhibits P-glycoprotein resulting in decreased hepatic metabolism and renal excretion of colchicine. Colchicine and CsA withdrawal as well as appropriate supportive treatments were effective to manage all of these complications.

A comparison of four algorithms for the measurement of interrupter respiratory resistance in adults.

The aim of our study was to compare four algorithms for the measurement of respiratory resistance in adults using the interrupter technique. Four methods to estimate alveolar pressure from the mouth pressure during occlusion were assessed in 122 normal adults (57 males, 65 females, aged 18-79 yr, mean 41.2 +/- 15.6): taking the mean oscillation pressure (Rint), performing a linear back extrapolation (RintL) or a linear regression for the whole curve (RintRL), taking the end-occlusion pressure (RintE). Mean values for Rint, RintL and RintRL in males were respectively 0.23 +/- 0.04, 0.22 +/- 0.04 and 0.22 +/- 0.04 kPa s L(-1), not statistically different. In females values were respectively 0.27 +/- 0.05, 0.26 +/- 0.05 and 0.26 +/- 0.05 kPa s L(-1), not statistically different. RintE was higher than the remainder and was the only measure correlating weakly with morphometric variables: RintE = 1.152 - (0.00152 x age (yr)) - (0.00382 x height (cm)), r = 0.31 (p < 0.05) in females; RintE = 0.227 - (0.00122 x age (yr)) + (0.00830 x body mass index (kg m(-2))) with r = 0.34 (p < 0.05) in males. We conclude that it is equivalent to estimate alveolar pressure from or extrapolating it to the beginning of occlusion in healthy adults but when taking the end-occlusion pressure, resistance is higher and depends in part on morphometric parameters.

Abysmal prognosis of patients with type 2 diabetes entering dialysis.

INTRODUCTION: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis. MATERIAL AND METHODS: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84). RESULTS: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients. CONCLUSION: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.