Update of the SFMV (French society of vascular medicine) guidelines on the conditions and safety measures necessary for thermal ablation of the saphenous veins and proposals for unresolved issues.

Venous insufficiency is a very common disease affecting about 25% of the French population (if we combine all stages of its progression). It is a complex disease and its aetiology has not yet been fully elucidated. Some of its causes are well known, such as valvular dysfunction, vein wall defect, and the suctioning effect common to all varicose veins. These factors are generally associated and together lead to dysfunction of one or more of the saphenous veins. Saphenous vein dysfunction is revealed by ultrasound scan, a reflux lasting more than 0.5 seconds indicating venous incompetence. The potential consequences of saphenous vein dysfunction over time include: symptoms (heaviness, swellings, restlessness, cramps, itching of the lower limbs), acute complications (superficial venous thrombosis, varicose bleeding), chronic complications (changes in skin texture and colour, stasis dermatitis, eczema, vein atresia, leg ulcer), and appearance of unaesthetic varicose veins. It is not possible to repair an incompetent saphenous vein. The only therapeutic options at present are ultrasound-guided foam sclerotherapy, physical removal of the vein (saphenous stripping), or its thermal ablation (by laser or radiofrequency treatment), the latter strategy having now become the gold standard as recommended by international guidelines. Recommendations concerning thermal ablation of saphenous veins were published in 2014 by the Société française de médecine vasculaire. Our society has now decided to update these recommendations, taking this opportunity to discuss unresolved issues and issues not addressed in the original guidelines. Thermal ablation of an incompetent saphenous vein consists in destroying this by means of a heating element introduced via ultrasound-guided venous puncture. The heating element comprises either a laser fibre or a radiofrequency catheter. The practitioner must provide the patient with full information about the procedure and obtain his/her consent prior to its implementation. The checklist concerning the interventional procedure issued by the HAS should be validated for each patient (see the appended document).

Characteristics of a molybdenum X-pinch X-ray source as a probe source for X-ray diffraction studies.

X-ray emission from a molybdenum X-pinch has been investigated as a potential probe for the high pressure states made in dynamic compression experiments. Studies were performed on a novel 300 kA, 400 ns generator which coupled the load directly to a low inductance capacitor and switch combination. The X-pinch load consisted of 4 crossed molybdenum wires of 13 µm diameter, crossed at an angle of 62°. The load height was 10 mm. An initial x-ray burst generated at the wire crossing point, radiated in the soft x-ray range (hυ < 10 keV). This was followed, 2-5 ns later, by at least one harder x-ray burst (hυ > 10 keV) whose power ranged from 1 to 7 MW. Time integrated spectral measurements showed that the harder bursts were dominated by K-alpha emission; though, a lower level, wide band continuum up to at least 30 keV was also present. Initial tests demonstrated that the source was capable of driving Laue diffraction experiments, probing uncompressed samples of LiF and aluminium.

Prenatal diagnosis of a rare de novo centromeric chromosome 6 variant.

Cytogenetic heteromorphisms are described as heritable variations at specific chromosomal regions without phenotypic effect. Polymorphisms of the size of heterochromatic centromeric regions of chromosomes 1, 9 and 16 have been well documented in humans but only four previous reports described centromeric polymorphism of chromosome 6. We present a prenatal diagnosis of a rare de novo centromeric chromosome 6 variant. Cytogenetic and molecular techniques were used to characterize this variant and confirm the de novo nature of this event. This case illustrates the importance of reporting unusual variant chromosomes for genetic counseling and for determination of the frequency of variant chromosomes in the general population.

Novel neuronal proteolipid protein isoforms encoded by the human myelin proteolipid protein 1 gene.

The human myelin proteolipid protein 1 gene (hPLP1), which encodes the major structural myelin proteins of the central nervous system (CNS), is classically described as expressed in the oligodendrocytes, the CNS myelinating cells. We identified two new exons in the intron 1 of the hPLP1 gene that lead to the expression of additional mRNA and protein isoforms mainly expressed in neurons instead of oligodendrocytes. Those novel neuronal PLP isoforms are detected as soon as human fetal development and their concomitant expression is specific of the human species. As classical PLP proteins, the novel protein isoforms seem to be addressed to the plasma membrane. These results suggest for the first time that PLP may have functions in humans not only in oligodendrocytes but also in neurons and could be implicated in axono-glial communication. Moreover, this neuronal expression of the hPLP1 gene might explain the neuronal dysfunctions in patients carrying hPLP1 gene mutations.

GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease.

BACKGROUND: Pelizaeus-Merzbacher-like disease (PMLD) is a genetically heterogeneous disorder within the group of hypomyelinating leukoencephalopathies. Mutations of the gap junction protein alpha 12 (GJA12) gene are known to cause one autosomal recessive PMLD form. Few patients with GJA12 mutated PMLD have been reported, and to date, the frequency as well as the genotypic and phenotypic spectrum of GJA12 related PMLD is unclear. METHODS: We report mutation analysis of the GJA12 gene in a clinical and radiologic well-characterized multiethnic cohort of 193 patients with PMLD from 182 families. RESULTS AND CONCLUSIONS: Only 16 patients (8.3%) from 14 families (7.7%) carry GJA12 mutations including five families where we detected only one mutated allele. Among those, we identified 11 novel alterations. Thus, GJA12 mutations are a rather rare cause for Pelizaeus-Merzbacher-like disease. The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1 (PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.

Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies.

The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein alpha12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation.

The effect of genotype on the natural history of eIF2B-related leukodystrophies.

BACKGROUND: Recessive mutations in the five eucaryotic initiation factor 2B (eIF2B) subunits have been found in leukodystrophies of variable age at onset and severity. OBJECTIVES: To evaluate the clinical spectrum of eIF2B-related disorders and search for a phenotype-genotype correlation. METHODS: Ninety-three individuals (78 families) with an undetermined leukodystrophy were selected on MRI-based criteria of childhood ataxia with central hypomyelination/vanishing white matter (CACH/VWM) for EIF2B genes analysis. RESULTS: Eighty-nine percent of individuals with MRI criteria of CACH/VWM have a mutation in one of the eIF2B beta to epsilon subunits. For 83 individuals (68 families), 46 distinct mutations (90% missense) in four of the five eIF2B subunits (beta, gamma, delta, epsilon) were identified. Sixty-four percent were in the epsilon subunit, a R113H substitution was found in 71% of eIF2B epsilon-mutated families. A large clinical spectrum was observed from rapidly fatal infantile to asymptomatic adult forms. Disease severity was correlated with age at onset (p < 0.0001) but not with the type of the mutated subunit nor with the position of the mutation within the protein. Mutations R113H in the epsilon subunit and E213G in the beta subunit were significantly associated with milder forms. CONCLUSIONS: The degree of eIF2B dysfunction, which is involved in the regulation of protein synthesis during cellular stress, may play a role in the clinical expression of eIF2B-related disorders.

Inhibition of NF-kappaB-mediated gene transcription by the human A2B adenosine receptor in Chinese hamster ovary cells.

NF-kappaB is a transcription factor that plays a vital role in regulating inducible gene expression in immune and inflammatory responses. In view of the well documented effects of adenosine on immune and inflammatory responses, we have explored whether adenosine A1, A2B and A3 receptors regulate NF-kappaB activity in transfected Chinese hamster ovary (CHO) cells using a luciferase reporter gene construct. No increases in NF-kappaB activity were observed in CHO-A1, -A2B and -A3 cells stimulated with the non-selective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine. Elevating intracellular cyclic AMP (cAMP) levels using forskolin (direct activator of adenylyl cyclase) and rolipram (type IV, cAMP-specific phosphodiesterase inhibitor), inhibited NF-kappaB activity in CHO cells. Adenosine A2B receptor stimulation also inhibited NF-kappaB activity, whereas adenosine A1 and A3 receptor activation had no effect. These data reflect the known coupling of adenosine A2B receptors to increases in cAMP. In conclusion, adenosine A1, A2B and A3 receptors do not directly activate NF-kappaB in CHO cells. However, adenosine A2B receptor activation significantly inhibited NF-kappaB activity. Inhibition of NF-kappaB activity by the adenosine A2B receptor may contribute to the anti-inflammatory effects of adenosine.

Regulation of p42/p44 mitogen-activated protein kinase by the human adenosine A3 receptor in transfected CHO cells.

In this study we have investigated whether the human adenosine A3 receptor activates p42/p44 mitogen-activated protein kinase (MAPK) in transfected Chinese hamster ovary (CHO) cells (designated CHO-A3). The high affinity adenosine A3 receptor agonist IB-MECA (1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-beta-D-ribofuranuronamide) stimulated time (peak activation occurring after 5 min) and concentration-dependent (pEC50=9.0+/-0.2) increases in p42/p44 MAPK in CHO-A3 cells. Adenosine A3 receptor-mediated increases in p42/p44 MAPK were sensitive to pertussis toxin and the MAPK kinase 1 inhibitor PD 98059 (2'-amino-3'-methoxyflavone). The broad range protein tyrosine kinase inhibitor genistein and the phosphatidylinositol 3-kinase inhibitors wortmannin and LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) also blocked adenosine A3 receptor stimulation of p42/p44 MAPK. In contrast, inhibition of protein kinase C had no significant effect on adenosine A3 receptor-induced p42/p44 MAPK activation. IB-MECA (pEC50=10.1+/-0.2) also increased the expression of luciferase in CHO-A3 cells transiently transfected with a luciferase reporter gene containing the c-fos promoter. Furthermore, IB-MECA-induced increases in luciferase gene expression were sensitive to pertussis toxin, PD 98059, genistein, wortmannin and LY 294002. In conclusion, we have shown that the human adenosine A3 receptor stimulates p42/p44 MAPK and c-fos-mediated luciferase gene expression in transfected CHO cells.

Nosocomial pneumonia in mechanically ventilated patients, a prospective randomised evaluation of the Stericath closed suctioning system.

OBJECTIVE: To compare the ventilator-associated pneumonia (VAP) incidence rates in mechanically ventilated patients according to the type of endotracheal suctioning (closed versus open). SETTING: The Neurosurgery Intensive Care Unit of the Grenoble University Hospital, France. DESIGN: A prospective randomised study performed after a 6-month period of nursing personnel training. PATIENTS: One hundred four consecutive patients needing mechanical ventilation for more than 48 h were randomised into two groups. To be eligible, patients had to have no active infection or respiratory affection in their passes. In the Stericath group (S+, n = 54), patients were not disconnected from the ventilator during suctioning. The others were routinely managed (S-, n = 50). In both groups patterns of frequency and duration of suctioning were performed according to a standardised protocol. MEASUREMENTS: The non-adjusted incidence rate of VAP was lower for S+ than for S- (7.32 versus 15.89 per 1000 patient-days, p = 0.07). Multivariate analysis performed using the Cox model showed an adjusted risk of VAP 3.5 times higher in S- (95% CI: 11.00-12.33). The risk being 4.3 higher in patients receiving gastric acid secretion inhibitors (1.08-16.82). In non-censored cases (n = 76) length of ICU stay increased by an average of 16.8 days when VAP was present (p = 0.0008). No adverse effect due to Stericath use was noted and volume of tracheal aspirate was similar between groups (p = 0.178). CONCLUSION: The use of Stericath reduced the incidence rate of VAP without demonstrating any adverse effect.

Does noninvasive ventilation reduce the ICU nosocomial infection risk? A prospective clinical survey.

OBJECTIVE: To observe the nosocomial infection (NI) distribution in ventilated patients of a single intensive care unit (ICU) according to the kind of control of the upper airways: noninvasive positive pressure ventilation (NPPV) versus endotracheal intubation (ETI). SETTING: ICU of a general hospital. DESIGN: Prospective clinical and epidemiologic survey. PATIENTS: In the period December 1994-March 1997, 761 patients were included who needed mechanical ventilation for more than 48 h: 129 were ventilated by NPPV (NPPV group), 607 were intubated (ETI group) and 25 required intubation after a period of NPPV (NPPV-ETI group). MEASUREMENTS AND RESULTS: The data used were prospectively collected according to the NI epidemiologic surveillance protocol of "C. CLIN Sud Est, Réa Sud Est", France. NI included a ventilator-associated pneumonia (VAP), catheter-related infection, urinary tract infection and bacteremia. Occurrence of NI was estimated by the density of incidence. Covariate-adjusted NI and VAP risk factors were assessed by the Cox model. The incidence density of total NI was lower for NPPV than for ETI (14.2 versus 30.3 per 1000 patient-days, p < 0.01). The Cox model showed that the use of noninvasive ventilation, adjusted to the severity of illness (SAPS II), reduced not only the VAP risk (hazard ratio (HR) = 4.07) but also the NI risk (HR = 1.95). CONCLUSION: The use of NPPV reduces the risk of VAP and NI, compared to ETI, irrespective of the severity of the patient's illness.

Combined effects of hypocapnia and nicardipine on airway resistance: a pilot study.

OBJECTIVE: The aim of this study was to investigate the modification of the resistive inspiratory properties of the respiratory system associated with hypocapnia in the presence of nicardipine. METHODS: The resistance of the respiratory system, Rrsmin, was studied in two groups of patients who needed mechanical hyperventilation. Group 1 (n = 14; 47 years) was the control group (head injuries); group 2 (n = 12; 53.5 years) included patients treated over a 3 week period with nicardipine (0.5 microgram.kg-1.min-1 i.v.) to prevent arterial vasospasm after subarachnoid haemorrhage. RESULTS: There was no statistical difference between the groups concerning anthropometric and basal respiratory characteristics. In group 1, hypocapnia caused a 20.9% increase in Rrsmin, but no significant increase was observed in group 2. CONCLUSION: Hypocapnic alkalosis had a significant bronchial constrictory effect, which was eliminated in the presence of nicardipine hydrochloride.

Severe head injuries: an outcome prediction and survival analysis.

OBJECTIVE: To identify the predictors determined early after admission and associated with unfavorable outcome or early (within 48 h) death after severe head injury. DESIGN: Prospective cohort study. SETTING: A neurosurgical intensive care unit in a university hospital. PATIENTS: 198 consecutive comatose patients hospitalized from 1989 to 1992. RESULTS: Logistic regression showed that a combination of age, best motor response score from the Glasgow Coma Scale, and hypoxia provided a good prediction model of unfavorable outcome (sensitivity = 0.93). The length of participation of survivors was 6 to 61 months (median 27.1). The Cox model demonstrated age, motor score less than 3, mydriasis, and hypoxia as poor prognosis factors. CONCLUSIONS: Clinicians can determine the odds of a good outcome from the combination of three easily measurable factors using a simple diagram constructed from logistic regression. Survival analysis showed that motor score adjusted values greater than 3 had the same prognosis.

[Prediction of respiratory complications after surgery of the abdominal aorta]. / Prédiction des complications respiratoires après chirurgie de l'aorte abdominale.

The most frequent type of complication in patients undergoing aortic surgery is respiratory. Preoperative lung function (PFT) and arterial blood gas measurement (ABG) are often carried out to assess the risk more precisely. The aim of the present retrospective study was to determine which value of lung function test could identify patients who developed such complications. "Receiver Operating Characteristic" (ROC) curves and the area beneath the curve for the diagnosis of respiratory complications were calculated for each variable of PFT and ABG. The greatest Youden index for each variable was chosen as indicative pulmonary function criterion of increased risk of pulmonary complications. One hundred and ninety-five patients (age: 65 +/- 10 years) were included. Respiratory complications occurred in 15% of patients. Respiratory complications increased from 12% if the vital capacity (VC) was > or = 77% of the predicted value to 35% if the VC was < 77% (P = 0.002), and from 10% if the FEV1 was > 76% to 34% if the FEV1 was > or = 76% (P = 0.0005). A decreased PaO2 or increased PaCO2 was not correlated with an increased incidence of respiratory complications. Length of stay in ICU or in hospital were increased when VC or FEV1 were low. Frequency of pulmonary complications was 9% in patients without PFT abnormalities, 16% in patients with either diminished VC or FEV1 and 35% in patients with both lowered VC and FEV1. However, all the areas under the ROC curves were < 0.7 and the sensitivity of the different variables was low. It is concluded that routine preoperative PFT and ABG cannot predict respiratory complications after abdominal aortic surgery.

Pulmonary function tests predict outcome after cardiac surgery.

The aim of this study was to examine the value of systematic preoperative pulmonary function tests (PFTs) in order to reliably predict prolonged stay in I.C.U., prolonged mechanical ventilation and mortality in elective cardiac surgical patients. 149 consecutive adult patients (valvular replacement or coronary bypass graft) were studied retrospectively. We examined the preoperative respiratory data: vital capacity (VC), first second forced expired volume (FEV1), PaCO2 and PO2. Length of stay in I.C.U. (LICU), duration of mechanical ventilation (DMV), incidence of reintubation and survival rate were used as indices of respiratory morbidity. The results of the present study clearly indicate that patients with impaired airway flow rates had a prolonged postoperative recovery following cardiac surgery. Mortality, ICV and DMV increased when FEV1 was less than 1.5 L, VC was less than 2.5 L, or PaO2 was less than 8.5 kPa. Reintubation was associated with impaired flow rates. Pulmonary function tests appeared effective in predicting postoperative complications and the need for prolonged ventilatory support.

[Four cases of tracheoesophageal fistulas in adults in intensive care units]. / Quatre cas de fistules oeso-trachéales chez l'adulte en réanimation.

Four cases of tracheo-oesophageal fistulae following mechanical ventilation are reported. The determining factors, revealing signs, and palliative and curative treatment are discussed based on a review of the literature. In this series, the tracheotomy cannula provided good protection of the upper airways in three cases of upper fistulae. In the other case, the fistula was too close to the carena, requiring the use of high frequency jet ventilation. The management of low, large fistulae is more problematic concerning the choice of technique and timing of the operation.