Biomedical subjects
Publications and source records attributed to F Fourrier.
We report a case of fulminant hepatitis related to a primary Epstein-Barr virus (EBV) infection in an immunocompetent 15-year-old male patient. The main causes of fulminant hepatitis are viral infections, drugs, and autoimmune diseases. Primary Epstein-Barr virus infection is usually a benign, self-limited disease in pediatrics but can exceptionally be fatal.
The haemostatic system is greatly modified during severe infections. The early activation of coagulation is triggered by tissue factor expression and secondary fibrinolysis impaired by the upregulation of fibrinolysis inhibitors. This imbalance is a major cause of subsequent organ dysfunction. Natural anticoagulants (Tissue factor pathway inhibitor (TFPI), Antithrombin (AT), and Protein C (PC) are consumed or inhibited in this pathological process justifying a therapeutic supplementation with these inhibitors to improve sepsis-induced organ failure and mortality. No effect on the mortality rate could be documented in controlled studies using recombinant TFPI or AT concentrates but a biological interaction with heparin therapy could have biased the results. Treatment with recombinant activated PC was associated with a significant reduction in the mortality rate of severely ill patients. An increase in the rate of hemorrhagic adverse effects was observed with these compounds, justifying a strict observance of contraindications and of patient selection.
The haemostatic system is greatly modified during severe infections. The early activation of coagulation is triggered by tissue factor expression and secondary fibrinolysis impaired by the upregulation of fibrinolysis inhibitors. This imbalance is a major cause of subsequent organ dysfunction. Natural anticoagulants (Tissue factor pathway inhibitor (TFPI), Antithrombin (AT), and Protein C (PC) are consumed or inhibited in this pathological process justifying a therapeutic supplementation with these inhibitors to improve sepsis-induced organ failure and mortality. No effect on the mortality rate could be documented in controlled studies using recombinant TFPI or AT concentrates but a biological interaction with heparin therapy could have biased the results. Treatment with recombinant activated PC was associated with a significant reduction in the mortality rate of severely ill patients. An increase in the rate of hemorrhagic adverse effects was observed with these compounds, justifying a strict observance of contraindications and of patient selection.
OBJECTIVES: To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. METHODS: We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. RESULTS: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. DISCUSSION: During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. CONCLUSION: Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.
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AIM OF THE STUDY: To analyze the predictive value of computed tomography (CT) and initial physiologic and laboratory data findings in the immediate operative (OP) or non-operative (NOP) management of blunt liver injury (BL). METHODS: Eighty-eight BL, grade III (51), grade IV (28) and nine grade V (9), aged 26.2 years (16-75) were identified. Hemoperitoneum on CT, hemodynamic status, physiologic and laboratory data <24 hours or preoperative (transfusion, vascular filling) and follow-up >48 hours were analyzed. RESULTS: Data of 71/88 (80%) NOP and 17/88 (20%) OP patients were reviewed. A secondary laparotomy or laparoscopy was necessary in 11/71 TNO. Six OP (35%) and 1 NOP patients died. Blood units transfused were 1.33 (0-10) vs 5.9 (0-22) and vascular filling 1.45 (0.5-5.5) vs 3.6L (2-12) (P<10(-6), P<4.10(-3) respectively). NOP patients had less severe hemoperitoneum (31 vs 94%, P<10(-5)) and hemodynamic instability (8.5 vs 94%, P<10(-4)). But, there was an overlap of values of blood units transfused, amount of vascular filling and initial haemoglobin levels between NOP and OP patients and among CT grades of liver injury. No cut-off values could be determined: 33% NOP received >4 blood units and >3 L vascular filling; 30% had severe hemoperitoneum. In OP group 23.5% patients had lower values and no severe hemoperitoneum. CONCLUSION: In the management of BL, vascular filling and blood transfusion increased with the grade of CT liver injury and were globally more elevated in the operative group but did not individually correlate with hemodynamic stability and did not authorize, by themselves, to decide between operative versus non-operative management.
INTRODUCTION: Guillain-Barré Syndrome (GBS) is generally related to peripheral nervous system involvement, but certain variants with central nervous system manifestations have been described. CASE REPORT: In the present study we report 2 patients with GBS associated with hallucinations and onirism. Two men (age 64 and 49 years) presented GBS without proven infectious origin who required intensive care because of respiratory problems. The disease progressed and manifestations of encephalitis (hallucinations and onirism) appeared. The sensorimotor signs and encephalitis manifestations evolved in parallel with full recovery in the first patient and death after 11 months of intensive care in the second. CONCLUSION: GBS may be associated with stereotypic central nervous system symptoms, mimicking delirium tremens. The manifestations would be related to the severity of the initial period, but not to long-term prognosis.
An early diagnosis and heparin therapy have contributed to a decreased mortality in cerebral venous thrombosis (CVT). However, predictors of outcome are difficult to identify, because most studies suffered heterogeneity in diagnostic findings and treatments, retrospective design, and recruitment bias. The aim of this study was to evaluate the clinical outcome in 55 consecutive patients with CVT admitted over a 4-year period. The study population consisted of 42 women and 13 men, with a median age of 39 years (range 16-68). The diagnosis was performed with MRI in 53 patients, and angiography in 2. The outcome was assessed with the modified Rankin scale (mRs). After a median follow-up of 36 months (range: 12-60), 45 patients were independent (mRS 0-2), and 10 were dependent or dead (mRS 3-6). Of 48 survivors, 7 had seizures, 6 motor deficits, 5 visual field defects, 29 headache (migraine in 14, tension headache in 13, other in 2). The logistic regression analysis found focal deficits and cancer at time of diagnosis, as independent predictors of dependence or death at year 3, and isolated intra-cranial hypertension as an independent predictor of survival and independence. Mortality rates are low in the absence of cancer and focal deficits, and more than 80 % of survivors are independent after 3 years. However, 3/4 of survivors have residual symptoms. Therefore, despite a low mortality rate, CVT remains a serious disorder.
OBJECTIVE: To present and discuss the rationale and the results of clinical trials using supplementation with physiologic anticoagulants (Tissue Factor Pathway Inhibitor (TFPI), AntiThrombin (AT), and Protein C (PC) in patients with severe sepsis. RATIONALE: An early activation of the coagulation cascade occurs in severe sepsis. TFPI, AT, and PC are major inhibitors of the coagulation cascade, and additionally modulate inflammatory and vascular reactions. They are consumed or inhibited in the sepsis pathologic process. Therapeutic supplementation with these inhibitors could improve the sepsis-induced organ failures and mortality. CLINICAL RESULTS: Randomized controlled studies were recently completed. No effect on the mortality rate could be documented after treatment with recombinant TFPI. AT concentrates neither improve mortality, but a biological interaction with heparin therapy could have biased the study results. Treatment with recombinant activated PC (alpha-drotrecogin) was associated with a significant reduction in the mortality rate of severely ill patients and received recently the approval from FDA and EC authorities in this indication. An increase in the rate of hemorrhagic adverse effects has been observed with these compounds, justifying a strict observance of contraindications and of patients selection. PROSPECTIVE: Additional studies are needed to give confirmation of the positive effects of activated PC supplementation in less severely ill patients, children and specific clinical situations. The effects of new anticoagulant compounds are currently evaluated in preclinical studies.
OBJECTIVES: To describe five new cases of life-threatening cefepime-induced neurotoxicity observed in a 2-year period. SETTING: A university intensive care unit. PATIENTS: Five patients recently treated with cefepime, admitted for seizures and coma. All suffered from acute renal failure, induced by sepsis and combined aminoside therapy, or by cefepime itself in one case. INTERVENTIONS: All patients underwent hemodialysis, which led to complete neurological improvement in four of them. One patient remained comatose and subsequently died. MEASUREMENTS: Blood and CSF cefepime levels were measured by high performance liquid chromatography before and after hemodialysis. CONCLUSION: The frequency of cefepime-induced neurotoxicity is probably underestimated. Monitoring of renal function and close neurological survey in treated patients should allow an early diagnosis of this complication. Urgent hemodialysis seems the best therapeutic method to obtain a rapid neurological improvement.
BACKGROUND: Calcitonin (CT) is the most sensitive marker available for medullary thyroid carcinoma, but it lacks specificity. Procalcitonin is the precursor protein of calcitonin. Infections are known to be associated with elevations of procalcitonin. The aim of this study was to evaluate a new sensitive calcitonin assay in a large population and to study the assay specificity in two particular populations: patients with renal failure and patients hospitalized in intensive care units with a high procalcitonin level. METHODS: Using two immunometric assays (A and B) to detect only mature calcitonin, we evaluated the calcitonin level in 488 sera (46 stimulation tests) from 340 subjects. RESULTS: The clinical evaluation showed that the calcitonin concentrations obtained with the two assays were similar for all patients except those with high procalcitonin levels. Among the patients, 12% (n=13) had basal calcitonin concentrations greater than 10 pg/ml with method A and 25.7% (n=25) with kit B. No correlation was found between calcitonin and procalcitonin concentrations. CONCLUSION: The new sensitive calcitonin assay tested is very efficient especially for the low concentrations. The cross-reaction for high procalcitonin levels exists and is variable according to the kits used. The procalcitonin evaluation can help the interpretation of ambiguous calcitonin levels.
We examined the hypothesis that recombinant human antithrombin would reduce mesenteric venule leukocyte adhesion and small intestine injury in endotoxemic rats. Endotoxemic (endotoxin 10 mg/kg, intravenously) rats were treated either with saline or recombinant human antithrombin (250 and 500 U/kg). In some rats, indomethacin (100 mg/kg, intraperitoneally) was injected 60 min prior to endotoxin and recominant human antithrombin (500 U/kg) treatment. Compared to controls, intravital videomicroscopy of the mesentric venule showed an increase of leukocyte rolling (55+/-17 versus 70+/-19 leukocytes/min; P < 0.05) and firm adhesion (1.1+/-0.3 versus 5.8+/-0.8 leukocytes/100 microm; P < 0.05) in endotoxemic rats. Recombinant human antithrombin attenuated endotoxin-induced venular endothelium leukocyte adhesive cascade. The beneficial effects of recombinant human antithrombin on leukocyte adhesion were inhibited by indomethacin (100 mg/kg, intraperitoneally) in endotoxemic rats. Endotoxin treatment increased fluorescein isothiocyanate (FITC)-labeled dextran 4,000 (FD4) gut lumen to plasma ratio and wet weight/dry weight ratio. Recombinant human antithrombin (500 U/kg) attenuated endotoxin-induced gut injury. These observations suggest that recombinant human antithrombin reduces endothelium-leukocyte interactions in endotoxemic rats by interacting with local prostacyclin production.
OBJECTIVES: To document in intensive care unit (ICU) patients the effect of dental plaque antiseptic decontamination on the occurrence of plaque colonization by aerobic nosocomial pathogens and nosocomial infections. DESIGN: Single-blind randomized comparative study. SETTING: A 16-bed adult intensive care unit in a university hospital. PATIENTS: Patients consecutively admitted in the ICU with a medical condition suggesting an ICU stay of 5 days and requiring mechanical ventilation. INTERVENTIONS: After randomization, the treated group received dental plaque decontamination with 0.2% chlorhexidine gel, three times a day during the ICU stay. The control group received standard oral care. SPECIFIC MEASUREMENTS: Dental status was assessed by the Caries-Absent-Occluded index; the amount of dental plaque was assessed by a semi-quantitative plaque index. Bacterial sampling of dental plaque, nasal and tracheal aspirate, blood, and urine cultures were done on days 0, 5, 10, and every week. MAIN RESULTS: Sixty patients were included; 30 in the treated group and 30 in the control one (mean age: 51 +/- 16 years; mean Simplified Acute Physiological Score II: 35 +/- 14 points). On admission, no significant differences were found between both groups for all clinical and dental data. Compared with the control group, the nosocomial infection rate and the incidence densities related to risk exposition were significantly lower in the treated group (18 vs 33% days in the ICU and 10.7 vs 32.3% days of mechanical ventilation; P < 0.05). These results were consistent with a significant preventive effect of the antiseptic decontamination (Odds Ratio: 0.27; 95% CI: 0.09; 0.80) with a 53% relative risk reduction. There was a trend to a reduction of mortality, length of stay, and duration of mechanical ventilation. CONCLUSIONS: An antiseptic decontamination of dental plaque with a 0.2% chlorhexidine gel decreases dental bacterial colonization, and may reduce the incidence of nosocomial infections in ICU patients submitted to mechanical ventilation.
Inter-alpha-inhibitor (IalphaI) is a human plasma serine proteinase inhibitor. It contains one light peptide chain called bikunin that exerts antiproteinase activity and other antiinflammatory functions. Bikunin is covalently linked to two heavy chains that, after tissular diffusion, stabilize the extracellular matrix. Owing to its negative acute-phase reactant character and its susceptibility to proteolysis, IalphaI has been implicated in the pathophysiology of sepsis. Moreover, IalphaI has been shown to exert a protective effect on a pig model of endotoxic shock. Twenty patients admitted to the intensive care unit (ICU) for a septic syndrome were included in the present study. IalphaI and antithrombin III (ATIII) levels were measured on admission. Sequential measurements of IalphaI could be done in 4 patients. We demonstrate that IalphaI levels are significantly decreased in plasma samples collected on admission from patients with sepsis (59 +/- 32 mg/L vs 241 +/- 70 mg/L; P < .0001). This decrease was greater in severe sepsis and septic shock than in sepsis. Death was not predictable from initiol IalphaI levels. In 2 patients with a favorable course, IalphaI values regularly increased during the ICU stay. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis and microsequencing, we characterized IalphaI-related components in plasma from several patients; they obviously arise from IalphaI through proteolytic cleavage. Thus, systemic proteolysis and decreased biosynthesis both contribute to the fall in the plasma level of IalphaI. Because IalphaI is very sensitive to proteolysis by polymorphonuclear granulocytes (PMNs) that are stimulated during sepsis, we suggest that IalphaI plasma level would be a useful marker for neutrophil proteinase activity. ATIII, as well as IalphaI, is considered a negative acute phase protein. Because in vitro ATIII is less susceptible than IalphaI to proteolysis by PMNs and because their relative levels weakly correlated, we suggest that an unspecific systemic proteolysis is not significantly involved in the ATIII deficiency occurring in sepsis.
OBJECTIVE: To present and discuss the rationale and results of clinical trials using antithrombin (AT) supplementation in patients with sepsis. DATA SOURCES/STUDY SELECTION: Review of all controlled (open or double-blind) studies of patients with severe sepsis or septic shock who were treated with AT concentrates to obtain better control of coagulation activation and inflammation. DATA EXTRACTION: AT is a major inhibitor of the coagulation cascade. Recent experimental studies have also shown that it can modulate the inflammatory reactions that occur during sepsis. An early and prolonged decrease in AT activity is well documented during sepsis-induced disseminated intravascular coagulation and during the systemic inflammatory response. Thus, supplementation with AT concentrates has been proposed as a potential therapy in sepsis patients. DATA SYNTHESIS: Numerous uncontrolled studies of AT supplementation in sepsis patients have been reported in the last 20 yrs. Since 1993, four placebo-controlled randomized studies have been performed in France, Germany, Northwestern Europe, and Italy. Three of these studies were subjected to a meta-analysis of 122 patients. Results showed a nonsignificant 22% reduction in the 30-day all-cause mortality and a reduction in the length of stay in the intensive care unit in the AT treated group. The Italian study of 120 patients demonstrated that the overall mortality was similar in the placebo and treated groups. However, post hoc analysis according to the Cox regression model showed that in patients with septic shock, AT supplementation significantly decreased the risk of death. CONCLUSIONS: Together, these studies are consistent with the positive effect seen with AT supplementation in patients with severe sepsis. A multicenter phase III trial is currently in progress to definitively document its effect on mortality.
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OBJECTIVE: To assess the effect of endotoxin on cytochrome aa3 (Caa3) redox status in a controlled blood flow preparation of pig isolated hindlimb, at a constant oxygen delivery (Do2limb) (constant flow period) and during progressive ischemia (decreasing flow period). DESIGN: Randomized, controlled experimental study. SETTING: University hospital experimental laboratory. SUBJECTS: Ten piglets. INTERVENTIONS: Hindlimb blood flow was restricted to the femoral vessels. The arterial femoral blood flow coming from the carotid artery was controlled by a roller occlusive pump. The femoral venous blood flow was returned to the jugular vein. During the first 100 mins, the hindlimb blood flow was maintained at a normal level and then decreased stepwise. Animals were randomized to receive 150 microg/kg endotoxin lipopolysaccharide (LPS; n = 5) or saline (control; n = 5). MEASUREMENTS AND MAIN RESULTS: Hindlimb muscle Caa3 redox status was monitored by near-infrared spectroscopy. Hindlimb Do2limb and oxygen consumption (Vo2limb) were calculated. In the LPS group, a rapid reduction of Caa3 redox status was observed after LPS administration, whereas the hindlimb blood flow remained normal with no change in Do2limb and Vo2limb. A progressive simultaneous decrease in Do2limb and Vo2limb was observed during the decreasing flow period with no further reduction in Caa3 redox status. In the control group, no change was observed in Caa3, Do2limb, or Vo2limb during the constant flow period. During the decreasing flow period, Caa3 redox status was reduced as Do2limb and Vo2limb decreased. CONCLUSION: Our results suggest that endotoxin may induce a reduction of Caa3 redox status independently of Do2 and Vo2.
The Guillain-Barré syndrome is the most common cause of acute flaccid paralysis. The current mortality is 5%, while severe motor sequelae persist after one year in 10%. Multidisciplinary teams, trained in all specific treatments, are required to treat these patients. Oral and intravenous steroids have proved ineffective. Two large randomized clinical trials comparing plasma exchange (PE) with no treatment have shown a short-term and a 1-year benefit. The appropriate number of exchanges and the indications are now more precisely known. In the mild form (walking possible) patients should receive two PEs; a further two exchanges should be done in the event of deterioration or in advanced forms (loss of walking ability, mechanical ventilation). More exchanges are not beneficial. Recently two new randomized trials have produced evidence that intravenous immunoglobulin (IVIg) (0.4 g/kg/day for 5 days) was as effective as 5 PEs in advanced forms. The combination of PE with IVIg did not confer a significant advantage but increased the costs and risks. In advanced forms the choice between PE and IVIg depends on the contraindications for each treatment.