DNA vaccination for the priming of neutralizing antibodies against non-immunogenic STa enterotoxin from enterotoxigenic Escherichia coli

In order to test the use of DNA vaccination for its capacity to induce antibodies against the non-immunogenic heat-stable enterotoxin STa from Escherichia coli, BALB/c mice were immunized with plasmid DNA encoding hybrid proteins made by the insertion of wild type STa or insertion of the Cys6Ala, Cys17Ala and Cys6Ala-Cys17Ala STa mutants at positions 195 or 216 of the TEM-1 beta-lactamase. No STa specific antibodies could be detected after three plasmid injections, but a subsequent boost with native STa peptide was capable of inducing low levels of neutralizing antibodies, as tested in the suckling mouse assay. Highest STa specific responses were found in mice primed with the double mutated STa inserted in position 195. This plasmid induced highest T-cell responses to the TEM-1 protein, indicating that priming of helper T-cell responses to the carrier protein was essential. Mixed IgG1/IgG2a isotypes also reflected this T helper 1 type priming. Moreover, insertion into loop A of the TEM-1 carrier may be more suitable than insertion into loop B, because of reduced competition between carrier and hapten B cell responses.     

Therapeutic schedules influence the pattern of intellectual decline after irradiation of posterior fossa tumors

BACKGROUND: To evaluate intellectual decline in children with posterior fossa (PF) tumors treated with different therapeutic protocols. PROCEDURE: Forty children had a complete neuropsychological evaluation prospectively twice, at least 6 months year (y) after the end of their treatment. Patients were classified into four groups according to treatment schedules: Group 1 (n = 7) PF radiotherapy (PFRT) alone at 50 Gy; Group 2 (n = 13) reduced-dose cranio-spinal irradiation (CSI) at 25 Gy with a PF boost; Group 3 (n = 9) standard CSI at 35 Gy and a PF boost; and Group 4 (n = 11) high-dose chemotherapy with stem cell support followed by PFRT at 50 Gy. RESULTS: At the first evaluation (mean interval since diagnosis 3.7 y), the mean Full-Scale Intellectual Quotient (FSIQ) was 80 (SD = 19). Only patients in Group 1 had a normal mean IQ score of 92 (SD = 14). At the second evaluation (mean interval since diagnosis 6.3 y), the mean FSIQ scores were significantly lower with a mean difference of 2.4 points, i.e., a yearly decline of one point. The magnitude of the FSIQ decline was positively correlated with the first IQ score (P = 0.0001) and inversely correlated with age at diagnosis (P = 0.0005). A FSIQ decline was observed in all treatment groups except Group 1 (P = 0.005). The differences in FSIQ observed initially between the four treatment groups persisted at the second evaluation. CONCLUSIONS: This study shows that FSIQ continues to decline more than 4 years after the diagnosis but this yearly decline seems to decrease with time from diagnosis. Therapeutic schedules influence the magnitude of this decline. Long-term follow-up into adulthood is necessary to effectively adapt patient rehabilitation.     

Paris heat wave and oligohydramnios

OBJECTIVE: The objective of this study was to determine the frequency of oligohydramnios in term pregnancies during the Paris heat wave of 2003 (August 4-14). STUDY DESIGN: A comparison of this frequency to a historical control group examined during the same period in 2002. RESULTS: The frequency of oligohydramnios in normal term pregnancies was 17.5% during the heat wave that affected Paris in August 2003. CONCLUSION: This frequency was substantially higher than the rate of oligohydramnios in normal term pregnancies in August 2002 (4.4%).     

Clinical review: Corticotherapy in sepsis

The use of glucocorticoids (corticotherapy) in severe sepsis is one of the main controversial issues in critical care medicine. These agents were commonly used to treat sepsis until the end of the 1980s, when several randomized trials casted serious doubt on any benefit from high-dose glucocorticoids. Later, important progress in our understanding of the role played by the hypothalamic–pituitary–adrenal axis in the response to sepsis, and of the mechanisms of action of glucocorticoids led us to reconsider their use in septic shock. The present review summarizes the basics of the physiological response of the hypothalamic–pituitary–adrenal axis to stress, including regulation of glucocorticoid synthesis, the cellular mechanisms of action of glucocorticoids, and how they influence metabolism, cardiovascular homeostasis and the immune system. The concepts of adrenal insufficiency and peripheral glucocorticoid resistance are developed, and the main experimental and clinical data that support the use of low-dose glucocorticoids in septic shock are discussed. Finally, we propose a decision tree for diagnosis of adrenal insufficiency and institution of cortisol replacement therapy.     

Fabry disease: a review

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).     

A large para-renal PEComa

We report the case of a 45-year-old man with a voluminous para-renal mass. The tumor was composed of epithelioid or spindle-shaped eosinophilic and clear cells with some atypia and an elevated mitotic count. The immunohistochemical study was positive for anti-HMB45 antibodies and anti-actin-antibodies and negative for epithelial markers and PS100 antibodies. The diagnosis of epithelioid AML (PEComa) was established. Two years later, recurrence was observed with a voluminous mass in the left upper quadrant of the abdomen, with high cellular density and the same immunohistochemical features. This tumor belongs to the PEComa and is not easy to diagnose clinically and morphologically. The immunohistochemical phenotype is characteristic. AML are usually benign but some epithelioid AMLS outcome can be unfavorable with metastatic dissemination. Criteria of malignancy are not clearly defined in the literature. This case shows that the mitotic count and the tumor size are probably important.     

Maternal and neonatal outcome of 93 consecutive triplet pregnancies with 71% vaginal delivery

BACKGROUND: The aim of this study was to investigate neonatal and maternal data in a large series of triplet pregnancies as a function of the decision regarding the route of delivery. METHODS: A retrospective series of 93 triplet pregnancies managed and delivered between 1989 and 2001 in a single perinatal department was analyzed. Seventy-eight women with triplet gestations who underwent a trial of labor were compared with 15 women with triplet gestations who delivered their infants by elective cesarean delivery. Neonatal outcomes assessed included respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage and Apgar scores. Maternal outcomes assessed included preeclampsia, blood transfusion, endometritis and urinary tract infection. RESULTS: Sixty-six of 78 women (84%) who underwent a trial of labor had a successful vaginal delivery of all three neonates. The other 12 delivered their infants by cesarean delivery. Perinatal mortality referred to 104 triplet pregnancies was 48/1000. CONCLUSIONS: Our experience suggests that offering vaginal delivery is an acceptable management plan for triplet gestation in a center with a sufficient number of triplet deliveries.