[A new case of rare erythrocytosis due to EGLN1 mutation with review of the literature]. / Polyglobulie rare par mutation du gène EGLN1 : à propos d'un cas et revue de la littérature.

INTRODUCTION: The origin of polycythemia is often simple to detect. Sometimes it is necessary to look for hereditary forms, the decisive parameters being the dosage of erythropoietin and the measurement of the oxygen dissociation curve (P50). These rare diseases are related to high oxygen-affinity haemoglobins, abnormalities of the erythropoietin receptor or dysfunction of the HIF (hypoxia-inducible factor) pathway. CASE REPORT: We report the case of a 56-year-old patient with unexplained polycythemia associated with normal serum erythropoietin and normal P50, in whom the never previously described mutation c.400C>T(p.Gln134*) on exon 1 in the EGLN1 gene (encoding PHD2) was found. CONCLUSION: In the face of an unexplained polycythemia a good cooperation between clinicians and biologists is necessary to be able to characterize rare hereditary pathologies.

[Diagnostic workup in front of an atypical non hemolytic anemia]. / Démarche diagnostique devant une anémie « non hémolytique ¼ sans étiologie apparente.

The most potential causes of "non hemolytic" anemias are iron, folate or vitamin B12 deficiencies, severe renal impairment, endocrine diseases, inflammation and medullary disorders. In a non-exceptionnal way no cause is found, sometimes because of a wrong interpretation of analysis results and sometimes because of a little known etiology. The goal of this review is to point out analytical difficulties and to remember some rarer etiologies.

IgM peak independently predicts treatment-free survival in chronic lymphocytic leukemia and correlates with accumulation of adverse oncogenetic events.

We examined the significance of IgM peaks in chronic lymphocytic leukemia (CLL), including its association with newly reported MYD88, BIRC3, NOTCH1 and SF3B1 mutations. A total of 27, 25, 41 and 57 patients with monoclonal IgM or IgG peaks (IgM and IgG groups), hypogammaglobulinemia (Hypo-γ group) and normal immunoglobulin serum levels (normal-γ group) were, respectively, included. IgM peaks were mainly associated with Binet stage C and the del(17p). Biased usage of IGHV3-48 was shared by both IgM and IgG groups. IGHV3-74 and IGHV4-39 gene rearrangements were specific for IgM and IgG peaks, respectively. SF3B1, NOTCH1, MYD88 and BIRC3 mutation frequencies were 12%, 4%, 2% and 2%, respectively, being over-represented in IgM, IgG and Hypo-γ groups for SF3B1, and being equal between normal-γ and IgM groups for MYD88. Overall, 76%, 87%, 49% and 42% of cases from IgM, IgG, Hypo-γ and normal-γ groups had at least one intermediate or poor prognosis genetic marker, respectively. By multivariate analysis, IgM peaks were associated with shorter treatment-free survival independently from any other univariate poor prognosis biological parameters, including IgG peaks, Hypo-γ, IGHV status, SF3B1 mutations, cytogenetics and lymphocytosis. Therefore, as with IgG peaks, IgM peaks aggravated the natural course of CLL, with increased accumulation of adverse genetic events.

[Evaluation of outcome of patients hospitalized after pre-hospital cardiac arrest]. / Evaluation des patients hospitalisés au décours d'un arrêt cardiaque extrahospitalier.

The aim of this study was to assess management of patients resuscitated after pre-hospital cardiac arrest, initially indicated to preserve neurological status, the aetiological investigation only being undertaken when the outcome is favourable. Eighty-nine pre-hospital cardiac arrests were analysed retrospectively. The hospital survival was 16%, death being due to neurological lesions (55%), uncontrollable haemodynamic instability -39%) or other causes (7%). One year after the initial episode, none of the survivors had died, all living autonomously without (8 patients) or with minimal neurological sequellae (5 patients). These results are concordant with reports in the literature. The 11 cases of cardiac arrest with a favourable outcome of presumed cardiac origin underwent coronary angiography (6 cases) or endocavitary electrophysiological investigation (8 cases). These investigations showed or suggested an ischaemic process in 4 cases, an arrhythmia in 6 cases and severe valvular heart disease in 1 case. The independent predictive factors of survival were a Glasgow score of 6 or more on admission, the persistence of a light reflex and benign EEG appearances according to Synek's classification. The authors conclude that these results are comparable to those reported in the literature with aetiological investigations reserved for cases of favourable neurological outcome. The investigations including coronary angiography and electrophysiological investigation are essential as shown by the diversity of the cardiac pathologies identified.

Extending inspiratory time in acute respiratory distress syndrome.

OBJECTIVE: To assess the short-term effects of extending inspiratory time by lengthening end-inspiratory pause (EIP) without inducing a clinically significant increase in intrinsic positive end-expiratory pressure (PEEPi) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Controlled, randomized, crossover study. SETTING: Two medical intensive care units of university hospitals. PATIENTS: Sixteen patients with early (< or =48 hrs) ARDS. INTERVENTION: We applied two durations of EIP (0.2 secs and extended) each for 1 hr while keeping all the following ventilatory parameters constant: FIO2, total PEEP (PEEPtot = applied PEEP + PEEPi), tidal volume, inspiratory flow, and respiratory rate. The duration of extended EIP was titrated to avoid an increase of PEEPi of > or =1 cm H2O. MEASUREMENTS AND MAIN RESULTS: Despite an increase in mean airway pressure (20.6 +/- 2.3 vs. 17.6 +/- 2.1 cm H2O, p < .01), extended EIP did not significantly improve PaO2 (93 +/- 21 vs. 86 +/-16 torr [12.40 +/- 2.80 vs. 11.46 +/- 2.13 kPa] with 0.2 secs EIP, NS). However, although the difference in PaO2 between the two EIP durations was <20 torr (<2.66 kPa) in 14 patients, two patients exhibited a >40 torr (>5.33 kPa) increase in PaO2 with extended EIP. Extended EIP decreased PaCO2 (62 +/- 13 vs. 67 +/- 13 torr [8.26 +/- 1.73 vs. 8.93 +/- 1.73 kPa] with 0.2 secs EIP, p < .01), which resulted in a higher pH (7.22 +/- 0.10 vs. 7.19 +/- 0.09 with 0.2 secs EIP, p < .01) and contributed to a slight increase in arterial hemoglobin saturation (94 +/- 3 vs. 93 +/- 3% with 0.2 EIP, p < .01). No significant difference in hemodynamics was observed. CONCLUSION: In patients with ARDS, extending EIP without inducing a clinically significant increase in PEEPi does not consistently improve arterial oxygenation but enhances CO2 elimination.

Carbamazepine-associated severe left ventricular dysfunction.

INTRODUCTION: The cardiovascular effects of carbamazepine are well-known but left ventricular dysfunction is rarely reported. CASE REPORT: We describe 2 cases of severe carbamazepine-associated left ventricular dysfunction during massive self intoxications in young patients without preexistent cardiac disease. We compare our cases to the available literature and discuss the mechanisms implied in the development of left ventricular dysfunction following carbamazepine overdose. Bedside echocardiography was useful in both diagnosis and treatment.

Acute benzodiazepine withdrawal delirium after a short course of flunitrazepam in an intensive care patient.

Acute benzodiazepine and opioid withdrawal syndromes are increasingly described in intensive care unit patients. There is often some difficulty in distinguishing between the respective responsibilities of the sedative and analgesic agents. We report a case of acute benzodiazepine withdrawal delirium after a short course of flunitrazepam in an intensive care patient. Flunitrazepam was administered because of institution of mechanical ventilation. Recent data on the incidence and risk factors of the syndrome in intensive care unit patients are presented. Criteria for diagnosis and therapeutic guidelines are discussed.

[Use of the helium-oxygen mixture in pneumology practice]. / Utilisation du mélange hélium-oxygène en pratique pneumologique.

Therapeutic use of the helium-oxygen mixture (heliox) was first reported in 1934. Medical use was further restricted to physiological studies. Density and viscosity of Heliox are very different from those of air or oxygen. This can explain how Heliox can induce modifications in the airway flow. In diseases of the main or small airways (upper airway obstruction, chronic obstructive pulmonary disease, asthma), such modifications could induce a diminution in the resistive component of the work of breathing and therefore protect against the risk of developing a respiratory failure. This explains a renewed interest of clinicians for Heliox since the beginning of the eighties. To date, the good tolerance of heliox seems to be well established. Inversely, scientific validation of the therapeutic indications of the mixture in airway diseases are lacking. Moreover, potential therapeutic indications of the mixture are not restricted to airway diseases. Various applications, such as adult respiratory distress syndrome, pneumothorax, fiberoptic bronchoscopy, and mechanical ventilation, are suggested by preliminary reports. Obtaining a synthetic vision of older and more recent studies is the purpose of this review.

Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection.

To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested whether the five proteins were predictors of clinical severity, which was evaluated by simplified acute physiological score (SAPS), number of organ failures (MOF), acute lung injury (ALI), and subsequent final outcome. Levels of the five plasma markers were higher in patients with severe infection (n = 25) than in patients without sepsis (n = 7) and healthy volunteers (n = 9). In the study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for nonsurvivors as well as for patients with septic shock or with bacteremia, and they were correlated with SAPS and MOF. Survival outcome was predicted with high sensitivity and specificity by initial plasma levels of sICAM-1 and vWf:Ag. The initial sICAM-1 level appeared to be an independent prognostic variable, based on a logistic regression analysis. Unlike sE-selectin, sICAM-1 remained at high levels indefinitely in nonsurvivors. We conclude that, unlike neutrophil activation markers, levels of endothelium-derived soluble adhesion molecules and vWf:Ag in severe sepsis syndrome are correlated with the severity of illness and may be considered as predictors of survival outcome.

[Long-term survival after extra-hospital cardiac arrest]. / Survie à long terme après arrêt cardiaque extra-hospitalier.

Survival rate after out-of-hospital cardiac arrest varies according to evaluation criteria. It can be estimated that in 22 to 63% of the cases, effective hemodynamic performance is restored although hospital mortality is much higher, reaching 63%. Death, frequent after prolonged cardiac arrest, is usually due to recurrent cardiac arrest or the effects of prolonged anoxia. Mortality in patients who survive the hospitalization period is approximately 20% during the year following discharge. Consequently one year after out-of-hospital cardiac arrest, only 5% of the patients are still alive. The quality of life varies greatly in these survivors; the course of neurological sequellae may be favorable in approximately half but leads to death in others. The primary factor predicting survival is the underlying pathology, highly influenced by age. Inversely, factors predicting a more favorable outcome include ventricular tachycardia as the origin of cardiac arrest, presence of other people at onset and rapid recovery of spontaneous hemodynamic activity. Loss of consciousness for more than 24 hours, defective bulbar reflexes and anomalies on the electroencephalogram are signs of gravity as are high blood glucose, major brain edema and abolition of somesthesic and auditive evoked potentials.

[Significance of lymphoplasmocytic infiltration in arrhythmogenic right ventricular dysplasia. Apropos of 3 own cases and review of the literature]. / Signification des infiltrats lymphoplasmocytaires dans la dysplasie ventriculaire droite arythmogène. A propos de 3 cas personnels et d'une revue de la littérature.

Three patients with typical histological signs of arrhythmogenic right ventricular dysplasia progressed to fulminating heart failure in 1 case and unexplained sudden death in the other two. There were signs of superacute myocarditis in the first case, previous healed pericarditis in the second and chronic myocarditis in the third case. These cases suggested the presence of an inflammatory process complicating the substrate of the dysplasia. Arrhythmogenic right ventricular dysplasia seems to be a developmental defect which is complicated in 50 to 70% of patients, according to a review of 74 cases reported in the literature, by a varying degree of myocarditis suggesting particular susceptibility of these patients to infection and explaining the presence of unusual amounts of fibrous tissue in some and the so called "progressive" nature of the disease in other patients.

Toxoplasma pericarditis in acquired immunodeficiency syndrome.

Large pericardial effusions are now a well-known complication of the acquired immunodeficiency syndrome, mainly caused by mycobacterial disease. However, other etiologies can be found. We report a case of toxoplasma pericarditis without other parasitic localizations. Pericarditis is a very uncommon clinical feature during toxoplasmosis. Its diagnosis is often difficult to establish, particularly in immunocompromised patients. Nevertheless, its possible evolution to constriction or tamponade requires its consideration. New methods of rapid tissue cultures may be helpful and allow early specific treatment.

[Current humoral profile in acute severe asthma]. / Profil humoral actuel des asthmes aigus graves.

This study examined the relationships between acid-base disorders, hypoxemia, electrolyte imbalances, plasma adrenaline (Ad) and noradrenaline (NAd) in 94 patients with acute severe asthma. Criteria of inclusion were [PaO2 + PaCO2/.8] less than 140 mmHg when breathing air (FiO2 = 21%) and/or PaCO2 greater than or equal to 45 mmHg. PaCO2 was closely related to H+ in those patients with hypercapnia: H+ nmol/l = 0.88 PaCO2 + 4 (r 0.91 ; n = 61; p less than 0.001). However, among the 62 acidotic cases (pH less than or equal to 7.36), 24 were classified as respiratory, 22 as mixed and 16 as metabolic. A loose though highly significant relationship was found between PaO2 and PaCO2 (when breathing air). Blood lactate, which was 3.61 +/- 1.9 mmol/l (+/- SD), was not correlated with anion gap or H+, but was loosely related to PaO2 and kalemia. Ad (1.53 +/- 1.17 nmol/l) and NAd (5.85 +/- 3.44 nmol/l), measured at the time of admission in 27 patients (FIO2 = 21%), varied significantly from those of a control group (p less than 0.01). NAd was correlated with H+, lactate and especially PaCO2, whereas no correlation could be established for Ad with these factors or NAd values. On the average, kalemia, phosphatemia and calcemia were lowered. In conclusion, mixed and metabolic acidosis were more common in this study than in a previous personal series and were not necessarily associated with an increase in blood lactate. Drugs taken prior to hospitalization must be considered in the pathophysiology of hyperlactatemia, which appears to be one among several factors linked to NAd levels.

Partial purification of the maturation-promoting factor MPF from unfertilized eggs of Xenopus laevis.

A 200-fold purification of the maturation-promoting factor or MPF from unfertilized eggs of Xenopus laevis is reported for the first time. Purification was achieved by three successive column chromatographies on hydroxyapatite, trisacryl blue and L-arginine-agarose. The presence of MPF was assessed by the usual maturation criteria after injections of test material into immature stage VI unstimulated X. laevis oocytes: the precocious appearance of the maturation spot (within 45-120 min), the germinal vesicle breakdown, the presence of the first polar body and the second metaphase spindle. Purification was monitored by the decrease of the minimal amount of protein injected in a constant volume (50 nl) required to induce 50% frequency of germinal vesicle breakdown. This amount decreased from 500 ng in the crude extract to 2.5 ng in the 200-fold purified material. Analysis by SDS-PAGE of the crude extract showed about 40 Coomassie-blue-stained polypeptides with molecular masses ranging from 300 kDa to 20 kDa, whereas in the 200-fold purified MPF only 5 stained polypeptides were revealed, with molecular masses of 62, 53, 49, 39 and 37 kDa. In vitro phosphorylations for the detection of kinase activities for endogenous and exogenous substrates were monitored by analysis of autoradiograms of SDS-PAGE, after treatment of fractions with [gamma-32P]ATP. Only inactive fractions eluted from columns ahead of MPF, and fractions containing MPF activity were tested. Phosphorylation of numerous stained polypeptides was demonstrated in the crude MPF extract and exogenous substrates such as phosvitin, casein and histone type II-AS were also strongly phosphorylated. In the MPF fraction, purified on hydroxyapatite, a polypeptide of 53 kDa was more highly and specifically phosphorylated and the presence of kinase activities was observed for the above three exogenous substrates. In the 100-fold and 200-fold purified MPF, phosphorylation of endogenous substrates could not be shown and kinase activities for the above three substrates were drastically decreased as compared with the crude and purified MPF obtained after hydroxyapatite column chromatography. However, neither endogenous phosphorylations nor kinase activities with the above exogenous substrates could be shown in inactive fractions eluted ahead of MPF at the different purification steps. Some characteristics of the purified material are also described in this paper.