Cerebral infarction in eclampsia

OBJECTIVE: This study was undertaken to characterize the neuroimaging findings of cerebral edema associated with eclamptic seizures by use of diffusion-weighted magnetic resonance imaging (MRI). STUDY DESIGN: During the 3-year period ending March 2002, 27 nulliparous women with eclampsia were evaluated with diffusion-weighted MRI and apparent diffusion coefficient mapping. Those with findings of restricted diffusion suggestive of cytotoxic edema underwent neuroimaging again 6 weeks post partum. RESULTS: All but 2 of these 27 women (93%) had reversible vasogenic edema. Six were also found to have areas of cytotoxic edema consistent with cerebral infarction. Five of these 6 women had persistent imaging findings of infarction when studied post partum, however, without clinical neurologic deficits. CONCLUSION: The spectrum of cerebral lesions in eclampsia as seen with MRI varies from initially reversible areas of vasogenic edema that may progress to cytotoxic edema and infarction in up to a fourth of women.     

Determination of the peptide binding motif and high-affinity ligands for HLA-DQ4 using synthetic peptide libraries

Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease. Various human leukocyte antigen (HLA) associations for different subgroups of this heterogeneous disease have been found. For early-onset pauciarticular arthritis (now oligoarthritic JIA), a strong association with the HLA class II haplotype DQA1*0401/DQB1*0402 (DQ4) has been described. We determined the peptide-binding specificities of this HLA-DQ molecule by screening a synthetic acetylated nonapeptide amide library with one defined and eight random sequence positions. A characteristic binding motif could be deduced. By use of these data, we designed defined specific nonapeptides and identified high-affinity ligands binding to HLA-DQ4. The peptide binding motif of HLA-DQ4 is very similar to the motif of HLA-DQ7, also associated with oligoarthritic JIA. It is, however, different from binding motifs of neutral or protective HLA-DQ molecules. Our results further support the idea of differential peptide presentation in the pathogenesis of oligoarthritic JIA.     

Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial

OBJECTIVES: We tested the hypothesis that thinner-strut stents are associated with a reduced rate of restenosis when comparing two stents with different design. BACKGROUND: We have previously shown that, for two stents with similar design, the risk for restenosis is dependent on the strut thickness. It is unknown whether strut thickness preserves its relevance as a determinant of restenosis even in the presence of different stent designs. METHODS: A total of 611 patients with symptomatic coronary artery disease were randomly assigned to receive either the thin-strut ACS RX Multilink stent (Guidant, Advanced Cardiovascular Systems, Santa Clara, California) (strut thickness 50 microm, interconnected ring design; n = 309) or the thick-strut BX Velocity stent (Cordis Corp., Miami, Florida) (strut thickness 140 microm, closed cell design; n = 302). The primary end point was angiographic restenosis (> or =50% diameter stenosis at follow-up angiography). Secondary end points were the incidence of target-vessel revascularization (TVR) and the combined rate of death and myocardial infarction (MI) at one year. RESULTS: The incidence of angiographic restenosis was 17.9% in the thin-strut group and 31.4% in the thick-strut group, relative risk, 0.57 (95% confidence interval, 0.39 to 0.84), p < 0.001. A TVR due to restenosis was required in 12.3% of the thin-strut group and 21.9% of the thick-strut group, relative risk, 0.56 (95% confidence interval, 0.38 to 0.84), p = 0.002. No significant difference was observed in the combined incidence of death and MI at one year. CONCLUSIONS: When two stents with different design are compared, the stent with thinner struts elicits less angiographic and clinical restenosis than the thicker-strut stent.     

Placenta percreta in week 10 of pregnancy with consecutive hysterectomy: case report

Placenta percreta in early pregnancy is rare and has been documented in only a few cases. We report on a patient with abdominal pain in week 10 of pregnancy. Sonography revealed a defective embryonic development and the absence of a border line between trophoblast and myometrium, as well as invasive growth in the region of isthmocervical transition, so curettage was performed. Heavy bleeding at this stage made a hysterectomy necessary. Histological examination revealed a placenta percreta. Because of possible complications, the therapy of choice for a placenta percreta is a hysterectomy, as was performed in this case.     

Methamphetamine rapidly decreases mouse vesicular dopamine uptake: role of hyperthermia and dopamine D2 receptors

Multiple high-dose administrations of the dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular dopamine uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the purpose of this study was to determine if methamphetamine-induced effects in rats occur in mice and to elucidate mechanisms underlying these effects. Results reveal methamphetamine treatment rapidly decreased mouse striatal vesicular dopamine uptake; a phenomenon associated with a subcellular redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity. Both methamphetamine-induced hyperthermia and dopamine D2 receptor activation contributed to the stimulant-induced deficits in vesicular dopamine uptake. Unlike methamphetamine, the dopamine reuptake inhibitors, methylphenidate and cocaine, rapidly increased vesicular dopamine uptake. The implications of these phenomena are discussed.     

Regulation of the vesicular monoamine transporter-2: a novel mechanism for cocaine and other psychostimulants

The plasmalemmal dopamine (DA) transporter (DAT) is a principal site of action for cocaine. This report presents the novel finding that in addition to inhibiting DAT function, cocaine administration rapidly alters vesicular DA transport. Specifically, cocaine treatment abruptly and reversibly increased both the V(max) of DA uptake and the B(max) of vesicular monoamine transporter-2 (VMAT-2) ligand (dihydrotetrabenazine) binding, as assessed ex vivo in purified rat striatal synaptic vesicles. Selective inhibitors of the DAT (amfonelic acid and GBR12935), but not the plasmalemmal serotonin transporter (fluoxetine), also increased vesicular DA uptake. Moreover, DA depletion resulting from administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine had cocaine-like effects. Conversely, administration of the DA-releasing agent methamphetamine rapidly decreased vesicular uptake. Taken together, these data demonstrate for the first time ex vivo that cocaine treatment rapidly alters vesicular monoamine transport, and suggest that alterations in cytoplasmic DA concentrations contribute to stimulant-induced changes in vesicular DA uptake. Hence, the VMAT-2 may be an important target for developing strategies to treat not only cocaine addiction but also other disorders involving alterations in neuronal DA disposition, including Parkinson's disease.     

Engagement of the CD4 receptor inhibits the interleukin-2-dependent proliferation of human T cells transformed by Herpesvirus saimiri

Infection with Herpesvirus saimiri, a tumor virus of non-human primates, transformed human CD4⁺ T cell clones to permanent interleukin (IL)-2-dependent growth without need for restimulation with antigen and accessory cells. The IL-2-dependent proliferation of these cells was dramatically inhibited by soluble anti-CD4 whole antibodies, F(ab′)₂ and Fab fragments, and also by gp 120 of human immunodeficiency virus. The inhibition was not due to cell death and could be overcome by high concentrations of exogenous IL-2. Cell surface expression of CD4, and to a lesser degree the density of the IL-2 receptor α chain, were reduced upon anti-CD4 treatment. After long lasting (>12h) incubation with anti-CD4, abundance and activity of CD4-bound p56^lck were diminished while the free fraction of p56^lck remained unchanged. Since IL-2 binding to its receptor activated only the CD4-bound fraction of p56^lck, the IL-2-induced p56^lck activity was diminished after long-term CD4 ligation. Taken together, our results suggest a cross talk between CD4- and IL-2 receptor-mediated signaling via p56^lck.