Efficient induction of CD8 T-associated immune protection by vaccination with mRNA transfected dendritic cells

Dendritic cells are excellent targets for antigen-specific immune intervention. Here we attempted to introduce a CD8 T cell-dependent epitope into dendritic cells for presentation on major histocompatibility complex class I and induction of immunity. Murine bone-marrow-derived dendritic cells were subjected to electroporation with mRNA transcribed in vitro from a plasmid encoding lymphocytic choriomeningitis virus glycoprotein or enhanced green fluorescent protein under the control of a T7 promotor. The transfection efficiency of dendritic cells was 22 to 40%. Maturation was not inhibited by the electroporation. Dendritic cells electroporated with the appropriate antigen induced cell number-dependent in vitro proliferation in CD8 T cells expressing a transgenic receptor recognizing the 33 to 41 sequence of lymphocytic choriomeningitis virus glycoprotein in association with H-2Kb/Db, indicating correct synthesis, processing, and presentation of the epitope. Naive C57BL/6 mice vaccinated with electroporated dendritic cells and challenged with lymphocytic choriomeningitis virus were protected. Vaccination induced epitope-specific T cells as assessed by tetramer staining in blood and spleen. These results indicate that targeting dendritic cells with antigen-encoding mRNA can induce antigen-specific CD8 T cell responses as well as protective anti-viral immunity in vivo. Targeting dendritic cells with antigen-encoding mRNA may find wider application for immune intervention in disorders such as autoimmunity and cancer.     

Urticaria pigmentosa localized on radiation field

A woman previously treated by radiotherapy for a breast cancer developed urticaria pigmentosa mainly restricted to the irradiation field, without any systemic symptoms. Localized forms of urticaria pigmentosa are exceptional, and their triggering factors are poorly understood. Several hypotheses can be discussed in this peculiar observation, among which a direct role of radiotherapy in the occurrence of cutaneous lesions cannot be ruled out.     

Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation

BACKGROUND: Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to up to 7 different pathologies affecting specific tissues. Three of these disorders affect cardiac and/or skeletal muscles with atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden cardiac death as common features. RESULTS: A new LMNA mutation (1621C>T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. The two patients: the proband and his daughter, were affected and exhibited an atypical form of dilated cardiomyopathy with an unexplained left ventricle aneurysm revealed by ventricular rhythm disturbances without atrio-ventricular block. CONCLUSION: This finding reinforces the highly variable phenotypic expression of LMNA mutation and emphasizes the fact that LMNA mutations can be associated with different cardiac phenotypes.     

First-night effect in the chronic fatigue syndrome

Since the magnitude of the first-night effect has been shown to be a function of medical conditions and of settings in which polysomnographies are performed, it is essential to evaluate the habituation phenomenon in each case in order to determine the optimal recording methodology. A first-night effect was evidenced in certain cases of chronic fatigue syndrome, but not in others. To clarify this issue, a large group of patients with chronic fatigue syndrome who had no primary sleep disorders were selected and recorded for two consecutive nights in a hospital sleep unit. Several parameters, frequently associated with the first-night effect, were found to be influenced by the recording methodology: Total Sleep Time, Sleep Efficiency, Sleep Efficiency minus Sleep Onset, Sleep Onset Latency, Wake Time, Slow Wave Sleep, Rapid Eye Movement Sleep, Rapid Eye Movement Sleep Latency and Number of Sleep Cycles. Bland and Altman plots determined that the difference scores between the nights included a systematic bias linked to the order of recordings (first-night effect). Factorial analysis grouped the difference scores into three factors. No significant difference was observed between patients with generalized anxiety comorbidity and those with no psychiatric comorbidity, or between those with and without psychiatric comorbidity. Chronic fatigue syndrome must thus be added on the list of conditions where a clinically significant habituation effect takes place.     

Continuous psoas compartment block for postoperative analgesia after total hip arthroplasty: new landmarks,technical guidelines,and clinical evaluation

A computed tomographic scan was obtained in 35 patients to measure the depth and the relationship of the branches of the lumbar plexus to the posterior superior iliac spine projection and the vertebral column. In addition, we prospectively studied 80 patients scheduled for total hip arthroplasty who received a continuous psoas compartment block (CPCB) in the postoperative period. CPCB was performed after surgical procedures by using modified Winnie's landmarks and nerve stimulation. From 5 to 8 cm of catheter was inserted. Radiographs were obtained after injection of 10 mL of contrast medium. An initial loading dose (0.4 mL/kg) of 0.2% ropivacaine was injected, followed by continuous infusion of 0.2% ropivacaine for 48 h. The depth of the lumbar plexus and the distance between the lumbar plexus and the L4 transverse process were measured. Visual analog scale values of pain at 1, 12, 24, and 48 h were obtained at rest and during mobilization. Amounts of rescue analgesia were also recorded. Sensory blockade of the principal branches of the lumbosacral plexus was noted at 1 and 24 h, as were adverse events related to the technique. There was a significant difference between men and women in depth of the lumbar plexus (median values, 85 vs 70 mm for men and women, respectively). There was a positive correlation between the body mass index and skin-lumbar plexus distances. In contrast, there was no difference regarding the distance between the transverse process of L4 and the lumbar plexus. The catheter tip lay within the psoas major muscle in 74% of the patients and between the psoas and quadratus lumborum muscles in 22%. In three patients, the catheter was improperly positioned. At 1 h, sensory blockade of the femoral, obturator, and lateral femoral cutaneous nerves was successful in, respectively, 95%, 90%, and 85% of patients. At 24 h, these rates were 88%, 88%, and 83%, respectively. During the 48-h study period, median visual analog scale values of pain were approximately 10 mm at rest and from 18 to 25 mm during physiotherapy. Five patients received 5 mg of morphine at 1 h. Five cases of unilateral epidural anesthesia were noted after the bolus injection. We conclude that CPCB with 0.2% ropivacaine allows optimal analgesia after hip arthroplasty, with few side effects and a small failure rate. Before lumbar plexus branch stimulation and catheter insertion, anesthesiologists should be aware of the L4 transverse process location and lumbar plexus depth. IMPLICATIONS: Lumbar plexus depth is correlated with the patient's body mass index and differs between men and women, but this is not true of the lumbar plexus-transverse process distance. Considering new landmarks, a continuous psoas compartment block promotes optimal analgesia after hip arthroplasty, with few side effects.     

Hemodynamic and hormonal responses to the sudden interruption of caval flow: insights from a prospective study of hepatic vascular exclusion during major liver resections

Hepatic vascular exclusion (HVE) combines portal triad clamping and occlusion of the inferior vena cava. Although HVE has been performed for major liver resections during the last 2 decades, little is known about the mechanisms that explain its satisfactory hemodynamic tolerance. Consequently, we performed a comprehensive study of both hemodynamic and hormone responses to HVE. Twenty-two patients who underwent liver resection for secondary tumors developed in noncirrhotic livers were prospectively studied. Heart rate, arterial blood pressure, pulmonary artery pressure, mixed venous saturation, cardiac output, and left ventricular dimensions determined by transesophageal echocardiography were monitored in HVE patients. Blood concentrations of arginine vasopressin (AVP), epinephrine, norepinephrine, dopamine, and atrial natriuretic peptide and plasma renin activity (PRA) were measured before clamping; 5, 15, and 30 min after clamping; and 15 min after unclamping. Hemodynamic response to HVE was characterized by a significant (P < 0.05) decrease in left ventricular dimensions, fractional area change, and pulmonary artery pressure. We also observed a marked decrease in cardiac output (50%) and an increase in heart rate and systemic vascular resistance. After unclamping, there was peripheral vasodilation, assessed by a significant decrease in systemic vascular resistance from the preclamping value to unclamping. An acute and sustained increase in AVP and norepinephrine that returned to baseline after unclamping and the absence of modification in PRA concentrations were noted. The marked decrease in venous return that characterizes HVE is compensated for by an increase in vascular resistance secondary to an important activation of the AVP and sympathetic systems. The PRA system does not play an important role in maintaining arterial blood pressure during HVE. IMPLICATIONS: Hemodynamic and hormonal responses to the acute interruption of caval venous return to the heart were investigated in patients undergoing liver resection with hepatic vascular exclusion. A compensatory role for arginine vasopressin and sympathetic systems that provoked increased vascular resistance was demonstrated.