Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study

<p>Abstract</p> <p>Background</p> <p>The presence of antiphospholipid antibodies (APLA) in multiple sclerosis (MS) patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA.</p> <p>Methods</p> <p>A consecutive cohort of 24 subjects with relapsing-remitting (RR) MS were studied of whom 7 were in remission (Rem) and 17 in exacerbation (Exc). All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL), β2 glycoprotein I (β2GPI), Factor VII/VIIa (FVIIa), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE).</p> <p>Results</p> <p>In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p < 0.01, for all 6 target antigens. Interestingly, none of the MS patients had elevated plasma titers of IgG against any of the target antigens tested. Correlation analysis between MRI enhancing lesions and plasma levels of APLA revealed high correlation for aPC, aPS and aFVIIa (p ≤ 0.0065), a trend for aPE and aCL (p = 0.056), and no correlation for aβ2GP1. The strongest correlation was for aFVIIa, p = 0.0002.</p> <p>Conclusion</p> <p>The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.</p

Presumed and definite bacteremia in extremely low gestational age newborns

AIM: To explore risk patterns for presumed and definite, early and late neonatal bacteremia. METHODS: We studied 1106 extremely low gestational age newborns who survived until postnatal day 28. We defined early definite bacteremia as a positive bacterial culture in the first week and definite late bacteremia as a positive bacterial culture in week 2, 3 or 4. Bacteremia was presumed if antibiotics were given for more than 72 h despite negative blood cultures. RESULTS: Risk patterns did not differ much for presumed and definite bacteremia in the first postnatal month. While maternal and pregnancy characteristics were associated with early bacteremia, neonatal comorbidities, especially NEC, were the main antecedents/correlates of late bacteremia. All four categories of bacteremia were associated with younger gestational age and lower birth weight. Infants with presumed and definite bacteremia had similar distributions of days of ventilation and oxygenation. CONCLUSION: Definite and presumed late bacteremias have rather similar risk patterns, while those of early and late bacteremia differ appreciably. Paediatrica

Differential risk of non-Hodgkin's lymphoma in Italian patients with primary Sjogren's syndrome

OBJECTIVE: To assess the incidence of non-Hodgkin's lymphoma (NHL) and estimate the relative risk (RR) of developing lymphoproliferative complications in a large population of Italian patients with Sjögren's syndrome (SS) and to ascertain if any difference exists between the north and centre-south of Italy. METHODS: Differential relative risks of NHL were obtained by comparing the number of observed cases with cases identified on the basis of age-sex-time specific incidence rates extracted from regional cancer registries. RESULTS: Among the 331 patients with SS studied, 9 cases of NHL occurred, while no lymphoid malignancy appeared in patients with overlapping connective tissue disease (secondary SS) or in males with primary SS. As the number of NHL cases identified on the basis of the rate in the cancer registries would have been 0.27, the RR is 33.3 (p < 0.001). The incidence rate of NHL in Italian patients with SS is about 5.1/1000 person-years. 5.4/1000 per year in the north of the country and 4.8/1000 per year in the centre-south. The relative risks are, respectively, 34.7 and 32.5. CONCLUSION: Italian patients with primary SS have increased risk of developing NHL. In this group, the absence of a significant difference between the north and the centre-south of Italy contrasts with the higher incidence of NHL in the general population of northern regions and strengthens the direct connection between primary SS and NHL

Colonization of second-trimester placenta parenchyma

OBJECTIVE: The overtly healthy, nonpregnant uterus harbors bacteria, Mycoplasma and Ureaplasma. The extent of colonization remains elusive, as are relationships between isolated microorganisms, preterm labor and fetal inflammation. STUDY DESIGN: Biopsy specimens of chorion parenchyma from 1083 placentas delivered before the beginning of the 28th week of gestation were cultured, and the placentas were examined histologically. The frequencies of individual microorganisms and groups of microorganisms were evaluated in strata of processes leading to preterm delivery, routes of delivery, gestational age, and placenta morphology. RESULTS: Placentas delivered by cesarean section with preeclampsia had the lowest bacterial recovery rate (25%). Preterm labor had the highest rates, which decreased with increasing gestational age from 79% at 23 weeks to 43% at 27 weeks. The presence of microorganisms in placenta parenchyma was associated with the presence of neutrophils in the fetal stem vessels of the chorion or in the vessels of the umbilical cord. CONCLUSION: The high rate of colonization appears to coincide with phenomena associated with preterm delivery and gestational age. The presence of microorganisms within placenta parenchyma is biologically important

Antenatal antecedents of a small head circumference at age 24-months post-term equivalent in a sample of infants born before the 28th post-menstrual week

BACKGROUND: Little is known about the antecedents of microcephaly in early childhood among children born at extremely low gestational age. AIM: To identify some of the antecedents of microcephaly at age two years among children born before the 28th week of gestation. STUDY DESIGN: Observational cohort study. SUBJECTS: 1004 infants born before the 28th week of gestation. OUTCOME MEASURES: Head circumference Z-scores of \u3c-2 and \u3eor=-2, \u3c-1. RESULTS: Risk of microcephaly and a less severely restricted head circumference decreased monotonically with increasing gestational age. After adjusting for gestational age and other potential confounders, the risk of microcephaly at age 2 years was increased if microcephaly was present at birth [odds ratio: 8.8 ((95% confidence interval: 3.7, 21)], alpha hemolytic Streptococci were recovered from the placenta parenchyma [2.9 (1.2, 6.9)], the child was a boy [2.8 (1.6, 4.9)], and the child\u27s mother was not married [2.5 (1.5, 4.3)]. Antecedents associated not with microcephaly, but with a less extreme reduction in head circumference were recovery of Propionibacterium sp from the placenta parenchyma [2.9 (1.5, 5.5)], tobacco exposure [2.0 (1.4, 3.0)], and increased syncytial knots in the placenta [2.0 (1.2, 3.2)]. CONCLUSIONS: Although microcephaly at birth predicts a small head circumference at 2 years among children born much before term, pregnancy and maternal characteristics provide supplemental information about the risk of a small head circumference years later. Two findings appear to be novel. Tobacco exposure during pregnancy, and organisms recovered from the placenta predict reduced head circumference at age two years

Pregnancy Disorders That Lead to Delivery Before the 28th Week of Gestation: An Epidemiologic Approach to Classification

Epidemiologists have grouped the multiple disorders that lead to preterm delivery before the 28th week of gestation in a variety of ways. The authors sought to identify characteristics that would help guide how to classify disorders that lead to such preterm delivery. They enrolled 1,006 women who delivered a liveborn singleton infant of less than 28 weeks' gestation at 14 centers in the United States between 2002 and 2004. Each delivery was classified by presentation: preterm labor (40%), prelabor premature rupture of membranes (23%), preeclampsia (18%), placental abruption (11%), cervical incompetence (5%), and fetal indication/intrauterine growth restriction (3%). Using factor analysis (eigenvalue = 1.73) to compare characteristics identified by standardized interview, chart review, placental histology, and placental microbiology among the presentation groups, the authors found 2 broad patterns. One pattern, characterized by histologic chorioamnionitis and placental microbe recovery, was associated with preterm labor, prelabor premature rupture of membranes, placental abruption, and cervical insufficiency. The other, characterized by a paucity of organisms and inflammation but the presence of histologic features of dysfunctional placentation, was associated with preeclampsia and fetal indication/intrauterine growth restriction. Disorders leading to preterm delivery may be separated into two groups: those associated with intrauterine inflammation and those associated with aberrations of placentation

Letter of Intent from the Fourth Detector (“4th”) Collaboration at the International Linear Collider, INFN Lecce Internal Report, 2009.

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