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Biomedical subjects

B François

Publications and source records attributed to B François.

At least 19 recordsLinked to original sources

Reactivation of human herpesvirus type 6 in multiple organ failure syndrome.

Human herpesvirus type 6 (HHV-6) and cytomegalovirus (CMV) are known to interact with the production of cytokines. In this study, we sought to determine the incidence of HHV-6 and CMV reactivation during multiple organ failure syndrome (MOFS) and to evaluate the potential effects of viral replication on both the morbidity and mortality associated with MOFS. Viral reactivation was assessed by use of specific polymerase chain reaction (PCR) analysis of the serum samples obtained from 48 consecutive patients with MOFS (the MOFS group) and from 48 sex- and age-matched patients with <2 organ failures (the control group). In addition, HHV-6 replication was assessed in 106 blood donors (the normal group). The incidence of HHV-6 replication was higher in the MOFS group than in the control and normal groups (26 [54%] of 48 vs. 7 [15%] of 48 and 5 [5%] of 106, respectively; P<.0001), with apparently no influence on morbidity and mortality rates. In contrast, reactivation of CMV was found in a single patient. Further studies are needed to evaluate the pathogenesis of HHV-6 replication in critically ill patients.

Adolescent↗

[Hemophagocytosis during multiple organ failure: M-CSF overproduction or viral reactivation?].

OBJECTIVE: This study was aimed to assess the potential role of M-CSF and viral reactivation in the genesis of haemophagocytosis during the multiple organ failure (MOF) syndrome. METHODS: Twenty-five patients (mean age: 60 +/- 16 years; Apache II: 23 +/- 5) sustaining MOF with an unexplained thrombocytopenia were studied. In each patient, a bone marrow aspirate, serum M-CSF concentration, and a virological examination (Herpes viruses) were obtained on admission. In addition, 20 patients (mean age: 57 +/- 15 years; Apache II: 24 +/- 7) with at least two organ failures but no thrombocytopenia constituted the control group. Circulating M-CSF levels and the frequency of virus reactivation were compared between groups. RESULTS: Haemophagocytosis was diagnosed in 11/25 patients (44%). No viral reactivation was found. Serum M-CSF concentrations were higher in the presence of haemophagocytosis (699 +/- 242 vs 438 +/- 157 IU.mL-1; p < 0.05). Ferritin levels were also increased in the presence of a macrophage activation (3,258 +/- 2,807 vs. 520 +/- 280 mg.L-1; p < 0.0001). In contrast, both circulating M-CSF and ferritin levels were similar between thrombocytopenic patients with no hemophagocytosis and controls. CONCLUSIONS: This study confirmed the high incidence of haemophagocytosis in critically ill patients sustaining MOF. In this setting, circulating M-CSF levels were markedly elevated, whereas no Herpes viruses reactivation was found.

Aged↗

Comparison of multiplane transesophageal echocardiography and contrast-enhanced helical CT in the diagnosis of blunt traumatic cardiovascular injuries.

BACKGROUND: Multiplane transesophageal echocardiography (TEE) and helical computed tomography (CT) of the chest have been validated separately against aortography for the diagnosis of acute traumatic aortic injuries (ATAI). However, their respective diagnostic accuracy in identifying blunt traumatic cardiovascular lesions has not been compared. METHODS: During a 3-yr period, 110 consecutive patients with severe blunt chest trauma (age: 41 +/- 17 yr; injury severity score: 34 +/- 14) prospectively underwent TEE and chest CT as part of their initial evaluation. Results of both imaging methods were interpreted independently by experienced investigators and subsequently compared. All cases of subadventitial acute traumatic aortic injury were surgically confirmed. RESULTS: Seventeen patients had vascular injury and 11 had cardiac lesions. TEE and CT identified all subadventitial disruptions involving the aortic isthmus (n = 10) or the ascending aorta (n = 1) that necessitated surgical repair. In contrast, CT only depicted one disruption of the innominate artery. TEE detected injuries involving the intimal or medial layer, or both, of the aortic isthmus in four patients with apparently normal CT results who underwent successful conservative treatment. All cardiac injuries but two were identified only by TEE. CONCLUSIONS: In patients with severe blunt chest trauma, TEE and CT have similar diagnostic accuracy for the identification of surgical acute traumatic aortic injuy. TEE also allows the diagnosis of associated cardiac injuries and is more sensitive than CT for the identification of intimal or medial lesions of the thoracic aorta.

Adult↗

Intrathecal baclofen after traumatic brain injury: early treatment using a new technique to prevent spasticity.

BACKGROUND: In the early course of severe head trauma, the clinical value of intrathecal administration of baclofen to reduce autonomic disorders and spasticity has not been established. METHODS: We studied four patients (Glasgow Coma Scale score 3 or 4) with autonomic disorders and spasticity who failed to respond to conventional treatment during the early course of head injury. Baclofen (25 microg/mL) was infused continuously through an intrathecal catheter inserted at patient bedside and subcutaneously tunneled. When this treatment was successful, the spinal catheter was removed and surgically replaced by another catheter connected to a subcutaneous pump. Clinical follow-up was obtained at 6 months after the head injury. RESULTS: Mean delay for the initiation of intrathecal baclofen was 25 days (range, 21 to 31 days), and optimal dose was 385 +/- 185 microg/day. In all patients, the Ashworth score was consistently reduced (3.5 +/- 0.5 vs. 4.5 +/- 0.5 for upper limbs and 2 +/- 0.5 vs. 4.5 +/- 0.5 for lower limbs), as were both the frequency and intensity of autonomic disorders. The spinal catheters were used during a mean period of 9.5 +/- 1.7 days without complications. All three survivors were equipped with a programmable pump and had a lower Ashworth score at 6 months. Autonomic disorders had disappeared in two patients and remained modest in the remaining patient. CONCLUSION: Continuous administration of baclofen via the intrathecal route using this new technique seems to reduce autonomic disorders and spasticity during the early course of severe traumatic head injury.

Adult↗

Extrapericardial cardiac tamponade caused by traumatic retrosternal hematoma.

Cardiac tamponade is an uncommon complication of blunt chest trauma, resulting typically from hemorrhage into the pericardial space. We report a case of hemodynamic compromise secondary to an extrapericardial compression caused by the acute formation of a retrosternal hematoma associated with a sternal fracture. The patient was involved in a violent deceleration accident. Initially, he only complained of an anterior thoracic pain, but subsequently became restless, pale, and dyspneic. A severe hypotension associated with sinus bradycardia (45 bpm) rapidly occurred. Both jugular veins became markedly turgescent, but no significant pulsus paradoxus was noted. Echocardiography disclosed a large hematoma, compressing anteriorly both the right ventricular cavity and outflow tract. Surgical evacuation of the retrosternal hematoma related to a bifocal fracture of the manubrium was followed by instantaneous hemodynamic improvement. Regional extrapericardial tamponade secondary to the acute formation of compressive retrosternal hematoma is an unusual cause of circulatory failure after severe blunt chest trauma. Since conventional clinical signs associated with typical tamponade physiology may be lacking in this setting, echocardiography is ideally suited for early recognition of this unusual condition.

Accidents, Traffic↗

[Refractory shock after converting enzyme inhibitor administration. Usefulness of angiotensin II].

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are commonly used during the early phase after myocardial infarction but severe hypotension and shock have been described. CASE REPORT: A 42-year old woman underwent a conservative management for an anterior acute myocardial infarction, initially associated with a pulmonary edema. Two hours after the initiation of a treatment with ACE inhibitor administered orally (lisinopril, Zestril), a circulatory failure in conjunction with an acute renal insufficiency occurred. Right heart catheterization disclosed markedly decreased systemic vascular resistance in the presence of a preserved cardiac index. Repeated fluid challenges and intravenous administration of norepinephrine failed to improve the hemodynamic status. The refractoriness of shock raised the hypothesis of a dysregulation of the renin-angiotensin system, secondary to the treatment by ACE inhibitor. Accordingly, the patient was given angiotensin II intravenously (Hypertension) which markedly raised systemic vascular resistance, and result in subsequent regression of shock. The patient was discharged after an otherwise uneventful course. DISCUSSION: We reported a refractory shock to fluid challenges and norepinephrine after the first dose of ACE inhibitor during acute myocardial infarction. Regression of shock was possible only with angiotensin II.

Adult↗

Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome.

Sepsis syndrome (SS) is associated with depressed PAF acetylhydrolase, the enzyme responsible for the degradation of platelet activating factor. PAF acetylhydrolase is in a large part produced by macrophages, whose inadequate activation with haemophagocytosis is frequent in patients with SS. The aim of this study was to test the hypothesis that PAF acetylhydrolase levels could be affected in these critically ill patients, because of the large amounts produced by activated macrophages in vitro and in vivo in animal models. The levels of serum PAF acetylhydrolase were assessed in 90 SS patients, who were divided into three groups: patients with (n = 34) or without haemophagocytosis (n = 31), and patients without thrombocytopenia (n = 25) who were used as a control group. The number of organ dysfunctions was matched between patients with haemophagocytosis and controls. Normal reference values were obtained in 59 randomly selected blood donors. Circulating levels of PAF acetylhydrolase were significantly (p = 0.0001) decreased in patients with SS (57+/-3 nmol/ml/min, n = 90) when compared with healthy subjects (69+/-3 nmol/ml/min, n = 59). PAF acetylhydrolase levels were greater in the presence of a haemophagocytosis but without statistical significance (64.2+/-6.5 vs. 50.1+/-2.8:p = 0.25). Despite the fact that macrophagic activation stimulates the in vitro release of PAF acetylhydrolase, no difference was found between patients with or without haemophagocytosis. The mechanism and the role of the PAF acetylhydrolase reduction in SS patients remain to be determined.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Sensitive and specific determination of midazolam and 1-hydroxymidazolam in human serum by liquid chromatography-electrospray mass spectrometry.

A liquid chromatographic-mass spectrometric technique was designed for the determination of the anaesthetic benzodiazepine midazolam (MID) and its active metabolite 1-hydroxymidazolam (1-OHM), with the aim of conducting pharmacokinetic/pharmacodynamic studies. MID and 1-OHM were extracted from alkalinised (pH 9.5) spiked and clinical serum samples using a single step, liquid-liquid extraction procedure with diethyl ether-2-propanol (98:2, v/v). The chromatographic separation was performed on a Nucleosil C18, 5 microm (150x1 mm I.D.) column, using a gradient of acetonitrile in 5 mM ammonium formate, pH 3.0 as the mobile phase, delivered at a flow-rate of 50 microl/min. The compounds were ionised in the ionspray source of an atmospheric pressure mass spectrometer, fragmented by in-source collisions and the pseudomolecular and fragment ions detected in the selected ion monitoring mode. The recovery was between 79 and 87% for MID, between 83 and 87% for 1-OHM and 81.5% for methylclonazepam. The limit of detection was 0.2 microg/l for MID and 0.5 microg/l for 1-OHM, the limit of quantitation (LOQ) was 0.5 microg/l for both. Linearity was verified from these LOQs up to 2000 microg/l and the method was found accurate and precise over this range. It was successfully applied to a preliminary study to establish the concentration versus time curve of MID and 1-OHM in a patient administered midazolam by continuous infusion.

Anesthetics, Intravenous↗

[A rare cause of sudden death in young adults with "normal" heart: the Brugada syndrome].

BACKGROUND: Brugada syndrome is a rare condition causing sudden death in young adults due to unexpected sudden-onset ventricular fibrillation. Diagnosis is based on the presence of an ST depression in the anteroseptal territory and a right branch block. No underlying dysrhythmic condition or arrhythmogenic heart disease can be detected. CASE REPORT: A 15-year old boy with an uneventful past history experienced cardiocirculatory failure due to ventricular fibrillation during a sports competition. Cardiac arrest developed and resuscitation was initially successful but death ensued due to cerebral anoxia. Characteristic electrocardiographic signs and the presence of similar anomalies in a brother and an aunt led to the diagnosis of Brugada syndrome. DISCUSSION: Brugada syndrome is a recently discovered hereditary condition with a probably underestimated prevalence. Systematic family studies have demonstrated autosomal dominant inheritance. The characteristic electrocardiographic anomalies can be transitory and may be unmasked by sensitivization tests. The only currently effective treatment is the implantable defibrillator programmed to prevent sudden death by ventricular fibrillation.

Adolescent↗

[Transesophageal echocardiography for diagnosis of traumatic injuries to the major intrathoracic vessels in 150 patients: the effect of the learning curve].

OBJECTIVES: To evaluate the role of transoesophageal echocardiography (TOE) in the management of patients with suspected traumatic lesions of the thoracic aorta (TLA) and its branches; to assess the influence of the learning curve on the diagnostic accuracy of TOE for the identification of TLA. STUDY DESIGN: Retrospective study. PATIENTS: The study included 150 patients (age: 41 +/- 17; Injury Severity Scale score: 31 +/- 17) who were admitted during a 4-year period for severe blunt chest trauma and who underwent a TOE study. METHODS: TOE were performed with either a monoplane (n = 54) or a multiplane probe (n = 96). In all cases, TLA were confirmed by angiography, computed tomography, surgery, or necropsy. Initially performed routinely, angiography was subsequently indicated when the TOE study was inconclusive or when a disruption of supraaortic arteries was suspected. Echocardiographic studies were reviewed by an experienced reader who was unaware of the medical history and initial conclusions. To evaluate the influence of the learning curve on the diagnostic accuracy of TOE, these conclusions were compared with the initial interpretations. RESULTS: A TLA was recognized in 25 patients out of 150 (17%), and evidenced using TOE in 22 of them. Three false negative and two false positive TOE results (needless thoracotomy) were recorded. After a learning period, the rate of inconclusive TOE studies decreased (18/150 vs 7/150: P < 0.05) and no false positive finding was recorded. The sensitivity and specificity of TOE for the diagnosis of TLA were 88 and 100%, and positive and negative predictive values were 100 and 97%, respectively. CONCLUSIONS: TOE is an accurate imaging technique for the diagnosis of TLA located at the aortic isthmus. However aortography becomes essential when injuries of the aorta branches are suspected. A learning period is required to improve the specificity of TOE for this indication.

Adult↗

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.

Alleles↗

Traumatic pulmonary hernia: surgical versus conservative management.

The therapeutic management of lung herniation, an uncommon complication of severe blunt chest trauma, remains controversial. We report here on two cases of traumatic lung herniation with different, yet successful, methods of therapeutic management according to the particular anatomic types. Because of the threat of tension pneumothorax, incarceration, or strangulation of the lung parenchyma in mechanically ventilated patients, surgical reduction of intercostal pulmonary hernias with narrow necks is usually recommended. In contrast, supraclavicular pulmonary hernias secondary to clavicle-sternal dislocation may be treated conservatively with serial clinical and thoracic imaging follow-up including chest computed tomographic scan. In this anatomical type of lung herniation, favorable spontaneous evolution is frequently observed, presumably because of the presence of a larger thoracic wall defect together with the absence of associated perforating bone trauma. The efficacy of the therapeutic approach proposed herein remains to be confirmed by further experience.

Adult↗

Quantification of traumatic hemomediastinum using transesophageal echocardiography: impact on patient management.

STUDY OBJECTIVES: To determine whether the quantitative evaluation of hemomediastinum using transesophageal echocardiography (TEE) is predictive of the presence of a traumatic disruption of the thoracic aorta (TDA) or its branches in patients who have sustained severe blunt chest trauma. DESIGN: Retrospective study. SETTING: ICU of a tertiary referral teaching hospital. PATIENTS: Forty-one patients sustaining severe blunt chest trauma (32 men, nine women; mean age, 43+/-16 years; mean Injury Severity Score, 39+/-22) who underwent a TEE study were divided into two groups, patients with (group TDA+, n=15) or without (group TDA-, n=26) major vascular injury diagnosed using an alternative method such as aortography, surgery, or necropsy. The control group included 41 age- and sex-matched patients with an unremarkable TEE study performed to rule out an intracardiac source of emboli. INTERVENTIONS: The presence of hemomediastinum was quantitatively assessed by measuring the distances between the esophageal scope and anteromedial aortic wall (distance 1), and between the posterolateral aortic wall and left visceral pleura (distance 2) at the level of the aortic isthmus. An observer who was unaware of both medical history and final diagnosis measured the distances. MEASUREMENTS AND RESULTS: In group TDA+, TEE demonstrated aortic injuries in 13 patients, revealed an isolated hemomediastinum in one patient (ruptured intercostal arteries), and was unremarkable in the remaining patient, who sustained a disrupted right subclavian artery. No associated major vessel injuries were diagnosed in the group TDA- (normal aortograms). When compared to the control group, mean distances were greater in patients with chest trauma (distance 1=5.5+/-4.4 mm vs 2.7+/-0.8 mm, p=0.001; distance 2=3.8+/-5.0 mm vs 1.2+/-0.3 mm, p=0.02). The corresponding distances were even greater in group TDA+ when compared with group TDA- (distance 1=8.6+/-5.9 mm vs 3.7+/-1.5 mm, and distance 2=7.1+/-7.0 mm vs 2.0+/-1.7; for both differences, p<0.01). A threshold value of 5.5 mm for distance 1 or 6.6 mm for distance 2 had a sensitivity of 80%, a specificity of 92%, a positive and negative predictive value of 86% and 89%, respectively, for the diagnosis of underlying major vascular injury. CONCLUSIONS: TEE allows quantitative assessment of traumatic hemomediastinum. The presence of a large hemomediastinum requires further evaluation by aortography, even if the thoracic aorta appears normal during the TEE examination, in order to rule out an underlying major vascular injury which may be outside the field of view of the echocardiographer.

Adolescent↗