A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Indicated and non-indicated preterm delivery in twin gestations: impact on neonatal outcome and cost.

OBJECTIVE: To identify the etiology and impact of preterm delivery in twin gestations. STUDY DESIGN: Twin gestations delivered at 33.0 to 36.9 weeks were identified in a perinatal database, and categorized by indication for delivery. Deliveries were identified as indicated, or non-indicated (discretionary). Neonatal outcomes were measured by birth weight, length of stay, NICU admission, and ventilator utilization. Data were divided and analyzed by indicated or discretionary delivery, and gestational age at delivery. RESULTS: Analyzed were 3252 twin gestations (6504 infants), with 78% having indicated delivery. Of the 22% with discretionary delivery, nearly 40% required NICU admission. With each advancing week of gestation, there was a significant decrease in incidence of NICU admission and nursery days. CONCLUSION: The majority of preterm deliveries were indicated, though 22% were discretionary. It is vital to consider neonatal morbidity and costs related to gestational age when choosing discretionary delivery.     

Mandibular fracture not shown by axial computed tomography: Benefit of computed reformation

A 36-year-old man was brought to the emergency department after being assaulted. A mandible series showed a nondisplaced fracture through the angle of the mandible extending through the left third molar tooth. Axial slices from a nonhelical computed tomographic (CT) examination of the head as well as a helical CT examination of the mandible failed to demonstrate the fracture. The fracture was well shown, however, on sagittal CT reformations. Although CT is generally regarded as more sensitive than plain radiography for the detection of fractures, fractures may be overlooked by CT if examination in only one plane is performed.     

Focused helical appendiceal computed tomography: Technique and interpretation

This article reviews a focused helical appendiceal computed tomographic technique and discusses an approach to appendiceal computed tomographic interpretation.     

Determination of needed radiographic room capacity to serve an emergency department

This study describes a method for determining the number of radiographic rooms devoted to emergency radiology that would be required to keep mean patient waiting time at a desired level. A desired mean waiting time for patients must be determined. In our setting, a mean waiting time of 8 minutes resulted in few complaints. The waiting time then sets the required utilization rate of available capacity. Daily and hourly volume and variability in volume of examinations were measured over a 3-month period. This represents the demand. The needed number of rooms is determined by comparing demand with effective available capacity for different numbers of rooms. To maintain an 8-minute mean waiting time, 50% utilization of capacity is required. Mean demand on Sundays is 176 examinations. Five rooms are required, since this gives a 180-examination effective capacity. Using waiting time as the primary decision criterion for making capacity decisions in emergency radiology has several advantages: the method is easy to use, volume variability is taken into account, and the focus is on service to patients.     

Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut.

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.     

"Single-exposure" dual energy digital radiography in the detection of pulmonary nodules and calcifications

We studied the detectability of mineralized and non-mineralized simulated pulmonary nodules with dual energy digital radiography. "Soft tissue" and "bone" images (pixel size = 0.2 mm, 10 bits deep) were obtained with subtraction image processing after a single simultaneous exposure (100 kVp, 8 mAs, 17 mR skin exposure dose) of two storage phosphors with an interleaved 0.9 mm copper wafer. Three classes of paraffin-based nodules (0.5 to 3.0 cm) of varying mineral concentration (0, 120 and 190 mg/cm3 K2HPO4) were randomly positioned on the chest wall of two healthy volunteers to simulate calcified and non-calcified nodules. The average receiver operating characteristics (ROC) area of six readers (n = 2880 observations) showed that digital "bone" images (ROC area: 0.77 +/- 0.03) were significantly better (P less than 0.04) than conventional radiographs (OC Film, Lanex medium screens, 141 kVp, 19 mR skin exposure dose) (ROC area: 0.71 +/- 0.05) in detecting calcification in nodules. The unsubtracted digital images of lower kilovoltage were not superior to the 141 kVp conventional radiographs in a subgroup of two readers (ROC area: 0.73 +/- 0.02). Digital "soft tissue" images were equivalent to conventional chest radiographs in detecting soft tissue pulmonary nodules (ROC areas: 0.92 +/- 0.04 and 0.92 +/- 0.05, respectively.     

Immunization with a polyprotein vaccine consisting of the T-Cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis

Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.     

Renal expression of endothelial and inducible nitric oxide synthase, and formation of peroxynitrite-modified proteins and reactive oxygen species in Wegener's granulomatosis

To investigate the role of nitric oxide (NO) in glomerular inflammation, the expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was studied in conjunction with inflammatory cell influx, H2O2 production, and the formation of nitrotyrosines in renal biopsies from patients with Wegener's granulomatosis (WG). Renal cryostat sections from patients with WG (n=15) were stained by immunohistochemistry for eNOS, iNOS, endothelial cells (CD31), nitrotyrosines, polymorphonuclear cells (PMNs, CD15), and monocytes/macrophages (CD14, CD68). Production of H2O2 was identified by enzyme cytochemistry using diaminobenzidine. In control tissues, strong staining for eNOS was found in glomerular and interstitial tubular capillaries and cortical vessels. A significant reduction in eNOS expression was found in WG biopsies, which was associated with a reduction in CD31 expression. Expression of iNOS was found in infiltrating inflammatory cells, mainly located in the interstitium. H2O2-producing cells were detected in glomeruli and were abundantly present in the interstitium. Nitrotyrosine-positive cells, however, were almost exclusively found in the interstitium. It is concluded that renal inflammation in WG is associated with the induction of iNOS in inflammatory cells and the formation of nitrotyrosines. Expression of eNOS in glomerular capillaries is lost, most likely due to endothelial cell damage. These results suggest that decreased NO production by endothelial cells, in conjunction with increased NO production by iNOS-positive inflammatory cells, is involved in renal tissue injury in WG.     

Protective role of endothelial nitric oxide synthase

Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases.This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed.