Pathologic and laboratory correlation in microcephaly associated with prenatal cocaine exposure.

The Authors report a case where cocaine abuse during pregnancy assessed by drug analysis at various site was associated with foetal microcephaly. Foetal pathologic findings revealed anomalies in neuronal migration and in the vascular architecture in the brain. Such anomalies might be the result of prolonged exposure to cocaine in utero, aggravated by the high concentration of cocaine metabolites in the amniotic fluid over a prolonged period.     

Durability of the viable aortic allograft

Of 581 aortic allografts implanted since 1967, 421 were analyzed for structural deterioration. This series is unique in that it includes patients from the early allograft experience. All allografts were cleanly procured, antibiotic sterilized, and either stored at 4 degrees C for up to 8 weeks or frozen to liquid nitrogen temperatures with cryopreservation to preserve the viable cusp fibroblasts. There were 25 frozen mounted aortic valves with a median time to valve failure of 12.1 years, which was not significantly different from the 12.5-year period for 114 fresh free-sewn aortic valves. The median time to valve failure was 6.6 years for 90 fresh-mounted aortic valves and 8.6 years for 192 fresh-mounted mitral valves (p = 0.05). The difference between all mounted and unmounted grafts was significant (p = 0.0001). In all groups, viable fibroblasts were present in specimens explanted up to 5 years after the operation. All specimens returned after more than 10 years were almost totally acellular. Evidence of increased collagen, suggesting that the fibroblasts survive implantation and then gradually die, was present in all specimens. This series suggests that durability of the unmounted viable allograft for aortic valve replacement is greater than for other types of tissue valves. Pre-mounted allografts for aortic or mitral valve replacement have a median survival of 8 years and are not more durable than other tissue valves.     

In utero fetal cerebral intraparenchymal ischemia diagnosed by nuclear magnetic resonance

Fetal brain damage can have many causes, the most common being possibly asphyxia which is often associated with intrauterine growth retardation. Early recognition of cerebral lesions is important in guiding obstetrical management. A case of antenatal cerebral intraparenchymal ischemia diagnosed by nuclear magnetic resonance (NMR) earlier than cerebral ultrasound examination is reported. This case report indicates that NMR may be a useful tool for the early detection of cerebral impairment in severe fetal growth retardation.     

Failure of cervical fibronectin to predict premature delivery in a population of monofetal pregnancies with idiopathic preterm labor.

OBJECTIVE: The purpose of the study was to evaluate the correlation between the presence of cervical fibronectin in a high-risk population of women with symptoms of preterm labor and the occurrence of preterm delivery or the need for aggressive tocolysis. STUDY DESIGN: One hundred and thirty women presenting with symptoms of threatened preterm labor were included. Cervical sampling for detection of fibronectin was performed on admission and every day until discharge or delivery. Time to delivery, length of hospital stay, use of indomethacin, delivery before 37 weeks of GA, mean term of delivery and failure of tocolysis to prevent delivery were compared to fibronectin test results. Data were analyzed using Student's t-test for continuous variables and the chi(2) test or Fisher exact test for discrete variables. RESULTS: No correlation could be found between the results of fibronectin cervical sampling on admission and any of the outcome parameters studied. Test performances were low (sensitivity 28%, specificity 57%, positive predictive value 19%, negative predictive value 69%). Results were not modified when the findings of repeated tests were taken into account. CONCLUSION: Cervical fibronectin failed to discriminate a subgroup of symptomatic women delivering prematurely. The prognostic value of fibronectin testing was not better than clinical data in our series. This observation is in disagreement with previous studies on the diagnostic value of vaginal or cervical fibronectin in preterm labor.     

Facilitating roles of murine platelet glycoprotein Ib and αIIbβ3 in phosphatidylserine exposure during vWF–collagen-induced thrombus formation

Vessel wall damage exposes collagen fibres, to which platelets adhere directly via the collagen receptors glycoprotein (GP) VI and integrin α₂β₁ and indirectly by collagen-bound von Willebrand factor (vWF) via the GPIb-V-IX and integrin αIIbβ3 receptor complexes. Platelet–collagen interaction under shear stimulates thrombus formation in two ways, by integrin-dependent formation of platelet aggregates and by surface exposure of procoagulant phosphatidylserine (PS). GPVI is involved in both processes, complemented by α2β1. In mouse blood flowing over collagen, we investigated the additional role of platelet–vWF binding via GPIb and αIIbβ3. Inhibition of GPIb as well as blocking of vWF binding to collagen reduced stable platelet adhesion at high shear rate. This was accompanied by delayed platelet Ca²⁺ responses and reduced PS exposure, while microaggregates were still formed. Inhibition of integrin αIIbβ3 with JON/A antibody, which blocks αIIbβ3 binding to both vWF and fibrinogen, reduced PS exposure and aggregate formation. The JON/A effects were not enhanced by combined blocking of GPIb–vWF binding, suggesting a function for αIIbβ3 downstream of GPIb. Typically, with blood from FcR γ-chain +/− mutant mice, expressing 50% of normal platelet GPVI levels, GPIb blockage almost completely abolished platelet adhesion and PS exposure. Together, these data indicate that, under physiological conditions of flow, both adhesive receptors GPIb and αIIbβ3 facilitate GPVI-mediated PS exposure by stabilizing platelet binding to collagen. Hence, these glycoproteins have an assistant procoagulant role in collagen-dependent thrombus formation, which is most prominent at reduced GPVI activity and is independent of the presence of thrombin.     

Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant metalloporphyrin

Endotoxin (lipopolysaccharide [LPS]) is known to induce the production of tumor necrosis factor (TNF)-alpha and the induction of manganese superoxide dismutase (MnSOD). We have recently demonstrated that induction of TNF-alpha and MnSOD by LPS is mediated through different signal transduction pathways. In the current study, we investigated the role of reactive oxygen species (ROS) in the induction of TNF-alpha and MnSOD messenger RNAs (mRNAs) in human monocytes. Hypoxia (1% O2) inhibited the production of superoxide (O2-) and the induction of MnSOD, but not TNF-alpha, mRNA. Diphenylene iodonium (DPI), a potent inhibitor of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, had no effect on LPS induction of MnSOD mRNA, whereas it markedly inhibited LPS-induced O2- production. Neither hypoxia nor DPI had any effect on LPS activation of nuclear factor (NF)-kappaB. These results suggest that (1) ROS is important in the induction of MnSOD, but not TNF-alpha, mRNA by LPS, (2) ROS from sources other than NADPH oxidase is involved in LPS induction of MnSOD mRNA, and (3) ROS-mediated LPS induction of MnSOD mRNA is independent of NF-kappaB activation.