[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases]. / Variabilité phénotypique et corrélations génotype-phénotype des dystrophinopathies : contribution des banques de données.

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.

Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study.

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.

[Adult onset nemaline myopathy revealed by respiratory insufficiency]. / Révélation d'une myopathie à bâtonnets par une insuffisance respiratoire de l'adulte.

INTRODUCTION: We report a case of nemaline myopathy revealed in adulthood by a respiratory insufficiency. CASE REPORT: A 26-year-old patient, without past history, was admitted with respiratory and right cardiac insufficiency which appeared in a few days. There was a severe restrictive lung impairment with nocturnal hypoventilation. Minor skeletal abnormalities and areflexia suggested a congenital myopathy. Muscle biopsy revealed a nemaline myopathy. CONCLUSION: Respiratory insufficiency is common in nemaline myopathy with infancy or childhood onset, but very rare in adults. It may be explained by multiple mechanisms.

[Transient central diabetes insipidus during a valproic acid poisoning]. / Diabète insipide central transitoire au cours d'une intoxication à l'acide valproïque.

A 39-year-old man was hospitalized after divalproate self-poisoning. He presented coma requiring tracheal intubation and mechanical ventilation at 11 hours and central diabetes insipidus. Serum valproic acid concentration was 590 mg/l at 30 hours. Progressive improvement occurred after hydratation and administration of vasopressin.

A reappraisal of ICU and long-term outcome of allogeneic hematopoietic stem cell transplantation patients and reassessment of prognosis factors: results of a 5-year cohort study (2009-2013).

Epidemiology and prognosis of complications related to allogeneic hematopoietic stem cell transplant (HSCT) recipients requiring admission to intensive care unit (ICU) have not been reassessed precisely in the past few years. We performed a retrospective single-center study on 318 consecutive HSCT patients (2009-2013), analyzing outcome and factors prognostic of ICU admission. Among these patients, 73 were admitted to the ICU. In all, 32 patients (40.3%) died in ICU, 46 at hospital discharge (63%) and 61 (83.6%) 1 year later. Survivors had a significantly lower sequential organ failure assessment (SOFA) score, serum lactate and bilirubin upon ICU admission. Catecholamine support, mechanical ventilation (MV) and/or renal replacement therapy during ICU stay, a delayed organ support and an active graft versus host disease (GvHD) significantly worsen the outcome. By multivariate analysis, the worsening of SOFA score from days 1 to 3, the need for MV and the occurrence of an active GvHD were predictive of mortality. In conclusion, the incidence of HSCT-related complications requiring an admission to an ICU was at 22%, with an ICU mortality rate of 44%, and 84% 1 year later. A degradation of SOFA score at day 3 of ICU, need of MV and occurrence of an active GvHD are main predictive factors of mortality.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Unusual implication of biopsy forceps in outbreaks of Pseudomonas aeruginosa infections and pseudo-infections related to bronchoscopy.

Between January and April 2003, a sudden increase in positive respiratory tract specimens for Pseudomonas aeruginosa was observed in an intensive care unit of the University Teaching Hospital of Montpellier, France. Most of the strains were cultured from bronchoalveolar lavage fluid samples, suggesting that bronchoscopic procedures could be implicated. The relationships between isolates were investigated by antibiotyping and pulsed-field gel electrophoresis. Both phenotypic and molecular markers allowed identification of two consecutive nosocomial outbreaks of respiratory infections related to two different bronchoscopes. These two outbreaks implicated nine and seven patients, respectively. Four of these 16 patients had true infections and recovered with antibiotic therapy. Inspection of both bronchoscopes revealed a damaged internal channel caused by defective biopsy forceps. These defects led to improper cleaning and disinfection of the bronchoscopes despite adherence to all current reprocessing procedures. The two outbreaks were controlled after replacing the inner channels of the bronchoscopes and switching from use of re-usable to disposable biopsy forceps. These outbreaks emphasize the need to establish surveillance procedures for detecting contamination of bronchoscopes, and the importance of recording each endoscopic procedure to facilitate further investigations if needed.

[Appropriate medication prescribing in older people]. / Bon usage des médicaments chez le sujet âgé.

Drug-induced adverse effects are one of the main avoidable causes of hospitalization in older people. Numerous lists of potentially inappropriate medications for older people have been published, as national and international guidelines for appropriate prescribing in numerous diseases and for different age categories. The present review describes the general rules for an appropriate prescribing in older people and summarizes, for the main conditions encountered in older people, medications that are too often under-prescribed, the precautions of use of the main drugs that induce adverse effects, and drugs for which the benefit to risk ratio is unfavourable in older people. All these data are assembled in educational tables designed to be printed in a practical pocket format and used in daily practice by prescribers, whether physicians, surgeons or pharmacists.

Diaphragm kinetics during pneumatic belt respiratory assistance: a sonographic study in Duchenne muscular dystrophy.

The principal aim of this study was to demonstrate the usefulness of M-mode sonography as a noninvasive technique to evaluate diaphragm excursion. The secondary aim was to assess the efficacy of pneumatic abdomino-diaphragmatic belt ventilation in patients with Duchenne muscular dystrophy. Using M-mode sonography, we measured the amplitude of diaphragm excursion in seven patients with Duchenne muscular dystrophy in various positions (0 degrees, 45 degrees, 75 degrees ) with and without pneumatic abdomino-diaphragmatic belt respiratory assistance. The belt significantly increased mean amplitude of diaphragm excursion by 62% at 45 degrees and by 55% at 75 degrees, and increased mean tidal volume by 43.5% at 45 degrees and by 49% at 75 degrees. Two patients were unable to tolerate the horizontal position (0 degrees ) During quiet breathing without the belt, amplitude of diaphragm excursion and tidal volume were positively correlated at 45 degrees (r=0.81; P=0.027) and 75 degrees (r=0.75; P=0.05). There was a significant intra-individual correlation between these two parameters during belt use but no inter-individual correlation. Without the belt, thoracic posture had no significant effect on amplitude of diaphragm excursion, either in quiet or deep breathing. After overnight respiratory assistance, arterial oxygen pressure and arterial oxygen saturation increased significantly, and arterial carbon dioxide pressure decreased from 52+/-6.4 to 46.4+/-4 mmHg. The pneumatic abdomino-diaphragmatic belt significantly improved gas exchanges and ventilation by increasing diaphragm excursion, as was clearly shown by noninvasive M-mode sonography. Indeed, M-mode sonography may be helpful in pneumatic abdomino-diaphragmatic belt pressure adjustment.

Lymphocyte subpopulations in bronchoalveolar lavages of patients with sarcoidosis and hypersensitivity pneumonitis.

Sarcoidosis and hypersensitivity pneumonitis (HP) are two granulomatous pulmonary diseases, the former of unknown cause and the latter with known etiology. To compare these diseases, we practiced bronchoalveolar lavage on 16 patients with sarcoidosis, 6 with HP, 10 healthy nonsmokers, and 10 smokers with chronic bronchitis. Lymphocyte subpopulations were evaluated by four membrane markers: (1) The total cell count was very high in patients with HP compared with those with sarcoidosis and with healthy subjects. (2) The proportion of lymphocytes was higher in patients with HP than in those with sarcoidosis (P less than 0.02) and also higher in patients with sarcoidosis than in healthy subjects (P less than 0.001). (3) There were only a small number of B cells and of Fc-receptor bearing cells. (4) The lymphocytes identified by our techniques were mainly T cells in sarcoidosis and HP (68.4 +/- 3.5 percent and 76.8 +/- 3.6 percent, respectively), but the proportion of "active" E-rosette-forming cells was higher in sarcoidosis than in HP (28.1 +/- 2.5 percent vs 9.8 +/- 1.5 percent) and higher in patients with HP than in healthy subjects. These studies suggest that: (1) these two granulomatoses may be differentiated by this method, which might also be used for other pulmonary angiitis and granulomas; (2) cell-mediated immune phenomena play a major role in the pathogenesis of sarcoidosis, and conversely the finding of low active E-rosette proportions in HP limits the role of delayed-type hypersensitivity; and (3) the exact role of immunologic activation of bronchopulmonary macrophages, "presenting" antigen to T cells, for instance, must be evaluated.

Membranous tracheal rupture after endotracheal intubation.

BACKGROUND: Tracheobronchial rupture after tracheal intubation has been infrequently reported. We report 6 cases of membranous tracheal rupture after endotracheal intubation treated at our institution over 7 years. METHODS: Overinflation of the tracheal cuff was speculated to be a frequent cause of the tracheal damage because the lesion was always a linear laceration of the posterior membranous wall. The diagnosis was suspected on the basis of common signs such as subcutaneous emphysema, respiratory distress, pneumomediastinum, and pneumothorax. Fiberoptic bronchoscopy was the best means of confirming the diagnosis and determining the location and extent of the lesion. In 5 patients, extensive laceration with severe respiratory disorders required emergent repair through a right posterolateral thoracotomy. RESULTS: There were two postoperative deaths unrelated to the tracheal lesion. A patient with a small tracheal defect and favorable clinical presentation showed a rapid positive outcome after conservative treatment. CONCLUSIONS: Tracheal intubation-related airway ruptures are rare but probably underestimated. Early recognition and emergent repair are essential, because failure to do so could result in potentially lethal events.

Ambulatory home total parenteral nutrition.

Ambulatory total parenteral nutrition (TPN) at home was used in 85 patients within a 6-yr period. Indications include severe malabsorption, fistulas, anorexia nervosa, and malignancies. The median duration of home TPN (HPN) was 67 days (range: 30-4,155 days). HPN duration for patients with benign diseases was longer [357.12 days (range: 30-4,155 days)] than for cancer patients [93.54 days (range: 30-421 days)]. Under HPN, patients gained a good nutritional status with an increase of total protein (p less than 0.001) and serum albumin levels (p less than 0.001). Weight gain was also significant (p less than 0.001). The rehospitalization rate was low (7.8%), but it was higher when HPN lasted for more than 3 months (10.87% +/- 1.58%) compared with short-term HPN (5.69% +/- 1.25%). Metabolic complications were unusual, and rehospitalization was related to the oncological treatment and/or infectious complications. Therefore, ambulatory HPN is a nutritional support that can significantly improve the life of patients with alimentary failure. Moreover, HPN allows significant cost savings compared to the alternative of prolonged hospitalization.

[Right atrial thrombus--a complication of central venous catheters]. / Thrombus auriculaire droit---une complication des voies veineuses centrales.

We describe the development, in three days, of a pediculate mass hanging on the right atrial lateral wall in a 39-year-old woman with a subclavian venous catheterization. She was a current smoker and alcoholic but without drug addict. The hypothesis of a non valvular right atrial infective endocarditis was considered at first, but subsequent events directed the diagnosis towards a thrombus, which was resorbed by heparin. We discuss the incidence, the complications, the treatment and the differential diagnosis of thrombus caused by a central venous catheter. The prevention of right atrial thrombus caused by a central venous catheter depends on the position of the central venous catheter tip, either in the superior vena cava or at the superior vena cava-right atrium junction. A more distal position is a frequent source of thrombotic and embolic complications.

[New aspects of macrolides: contribution of roxithromycin]. / Aspects nouveaux des macrolides: apport de la roxithromycine.

Roxithromycin (RU 28965) is a new semi-synthetic derivative of erythromycin. Its antibacterial activity is of the same order as that of other macrolides, although its MIC's against Legionella pneumophila are lower. In double-blind comparative studies there was no significant difference in therapeutic effectiveness between roxithromycin and the reference antibiotics tested. However, this new macrolide exhibits exceptional pharmacological properties (prolonged half-life, excellent tissue penetration and intracellular activity), and it is very well tolerated both clinically and biochemically.

[Acute motor axonal neuropathy and aseptic meningitis due to Staphylococcus aureus endocarditis]. / Neuropathie axonale motrice aiguë et méningite aseptique révélant une endocardite à Staphylococcus aureus.

INTRODUCTION: Central nervous system complications are commonly described in Staphylococcus aureus endocarditis but peripheral nervous system involvement is rare. EXEGESIS: We report the case of a 65-year-old woman who had tetraparesia and aseptic meningitis revealing S. aureus endocarditis. The presence of purpura on the lower limbs led to an initial diagnosis of meningococcal meningitis. Tetraparesia was due to an acute motor axonal neuropathy. Anti-GM1 antibodies were negative. Meningitis and tetraparesia improved with antibiotic therapy. CONCLUSION: Acute motor axonal neuropathy may be a presenting symptom of S. aureus endocarditis.

[An association of Werdnig-Hoffman disease and pregnancy: apropos of an unusual case]. / Association maladie de Werdnig-Hoffman et grossesse: a propos d'un cas exceptionnel.

The authors describe the first case in the literature of pregnancy in a twenty year old patient suffering from Werdnig Hoffman's disease. This is pure progressive spinal muscular atrophy which involves respiratory and locomotor functions. It brings into consideration several problems of respiration and in particular of genetics to be considered in this case, and we report that pregnancy was well tolerated in the patient who had a severe physical handicap.

[Pneumococcal infections in intensive care. Retrospective 8 year study]. / Infections à pneumocoques en réanimation. Etude rétrospective sur 8 ans.

OBJECTIVE: The aim of this study was to analyze the clinical presentations and severity of S. pneumoniae infections requiring hospitalization in an intensive care unit and evaluate the incidence and severity of infections caused by penicillin-resistant strains. PATIENTS AND METHODS: This retrospective study reviewed cases in our intensive care unit from January 1989 through December 1996 including all patients with pneumococcal infection. RESULTS: The study included 102 patients, mean age 59.6 years. Pneumonia was the most frequent (83 cases) followed by bacteriemia (31 cases) and meningitis (15 cases). Mortality was high (43%) and influenced by age, simplified severity score, and presence of shock at admission. Antibiotic resistance appeared in 1991 and increased over the years reaching, in 1996: 24% for penicillin, 38% for macrolides, 20% for sulfamides, 19% for tetracyclins, and 14% for phenicols. Penicillin-resistance was not found to modify clinical expression nor severity of infection. Amoxicillin and third-generation cephalosporins were the most widely used antibiotics. CONCLUSION: Pneumococcal infections in intensive care patients are severe with high mortality. The emergence of more and more resistant strains has little clinical consequence on severity or treatment.

[Descending necrotizing mediastinitis. A diagnosis not to be ignored]. / La médiastinite descendante nécrosante. Un diagnostic à ne pas méconnaître.

BACKGROUND: Acute descending posterior mediastinitis is a very serious condition which can develop after common ear-nose-throat infections. Clinical manifestations are typical and must be recognized rapidly for early diagnosis. CASE REPORTS: We report two cases. In the first case, a 28-year-old man had a retropharyngeal abscess which fistulized into the left pleural cavity. Three operations were necessary to achieve cure and favorable outcome. In the second case, mediastinitis was diagnosed in a 39-year-old patient following a throat infection. Despite early surgery, outcome was fatal due to development of pericarditis and tamponnade. DISCUSSION: These two cases illustrate the variable course of descending mediastinitis and emphasize the importance of early medicosurgical cure. Treatment is based on intravenous antibiotics using a combination of 2 or 3 drugs at high doses in association with emergency surgery and extensive mediastinal washings. Despite well-conducted treatment, descending necrotizing mediastinitis may lead to a fatal outcome.

[Acquired cytomegalovirus infections in immunocompetent adults: 116 cases]. / Cytomégalovirose acquise de l'adulte immunocompétent. 116 observations.

OBJECTIVE: To analyse retrospectively the clinical, biological and epidemiological features of cytomegalovirus (CMV) infection in the immunocompetent host. PATIENTS AND METHODS: A retrospective study was conducted in 116 cases of CMV infection (74 inpatients, 42 out-patients) collected from 1981 to 1997 in a university hospital. Diagnostic was established on serological criteria in all cases. RESULTS: Fever was observed in all cases but one (mean duration: 21 days). The most frequent symptoms were headache (51%) and myalgia (46%). Splenomegaly was the most frequent sign (36%). Pulmonary interstitial opacities on chest x-ray were found in 8.5% of patients. Pulmonary (1 case) and neurological (2 cases) complications occurred. Concomitant HIV primary infection was observed in 2 patients. Mononucleosis and ALAT and LDH elevations were observed in 95%, 85% and 95% of cases respectively. Viremia was positive in 79% (30/38). pp65 antigenemia was useful to establish the diagnosis in 9 patients. Antibiotics were prescribed in 46% before diagnosis was established. CONCLUSION: CMV infection in the immunocompetent host is a frequent and rarely complicated disease. pp65 antigenemia should be evaluated more in this setting. Most hospitalizations due to this affection could be avoided.

[Community acquired pneumonias in the region of Montpellier. Increase of pneumococci with reduced sensitivity to penicillins]. / Pneumonies communautaires dans la région de Montpellier. Augmentation des pneumocoques de sensibilité diminuée aux pénicillines.

OBJECTIVES: Bacteriological data indicate that there is an increased incidence of Streptococcus pneumoniae strains with an intermediate sensitivity to penicillin. The goals of the present study was i) to investigate the profile of sensitivity of Streptococcus pneumoniae isolated from patients with bacterial pneumonia in the area of Montpellier and ii) to compare this profile with the findings of the national center registry to better appreciate geographical specificity. METHODS: Fifty-six patients with bacterial pneumonia were enrolled into the study. From September 1989 to March 1994, we performed bacterial sampling including blood cultures, protected brushes and bronchoalveolar lavage specimens. We examined the antibiotic sensitivity of the germs which were isolated. All patients were followed using clinical and radiological criteria. RESULTS: A precise bacteriological diagnosis was established in 83.6% of the population. Streptococcus pneumoniae was found in 47.2% of the samples. In 19%, the strains displayed an intermediate sensitivity to penicillin. All patients recovered. CONCLUSION: We found a higher rate of resistance to penicillin in Montpellier than the common rate of the national reference center in France. The location of Montpellier closed to the Spanish border might, at least in part, explain this difference.