Bacterial and Ureaplasma colonization of the airway: radiologic findings in infants with bronchopulmonary dysplasia

OBJECTIVE: We designed this retrospective study to compare radiologic findings in premature infants with bronchopulmonary dysplasia (BPD) in whom gram-positive cocci (GPC), gram-negative bacilli (GNB), or Ureaplasma urealyticum were colonized. Another objective was to correlate the radiologic findings of these patients with the clinical severity of BPD. STUDY DESIGN: We correlated serial tracheal aspirates with radiographic findings from 183 infants whose birth weight was < or = 1250 gm. BPD severity was assessed by oxygen dependency at 36 weeks of postconceptional age (36 w PCA) and at the time of discharge. Two radiologists independently scored films taken at birth and 1, 7, 14, 21, 28, and 35 days of life. RESULTS: Of the study population, 55% were male and 35% were black; 80% received surfactant and 69% received dexamethasone; 91% survived. GPC isolates from throat cultures were mainly Staphylococcus [corrected] epidermidis and Streptococcus haemolyticus. A superimposed GNB colonization was present in 37% of these infants. Most common isolates were Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. Sepsis caused by GPC developed in 16% of all patients; 7% had sepsis caused by GNB. Infants infected with GNB remained receiving oxygen at 36 w PCA and at the time of discharge twice as often as those noninfected. RADIOLOGIC FINDINGS: Hyperinflation, interstitial changes, and generalized or localized emphysema were prominent features throughout. Mean radiologic scores increased over time in a pattern similar among GPC, GNB, and U. urealyticum infected and noninfected infants. High radiologic scores were not predictive at any time of infants who needed supplemental oxygen at 28 days and at 36 w PCA. Infants infected with U. urealyticum were neither clinically nor radiologically different than noncolonized neonates. CONCLUSION: GPC, GNB, and U. urealyticum airway colonization is not associated with particular radiographic changes at any time. GNB-infected infants had the most severe BPD course, and yet they were radiologically indistinguishable from the other patients. U. urealyticum colonization does not result in more clinically severe BPD or demonstrate a unique radiologic course.     

Impairment and disability: their relation during stroke rehabilitation

Migration of non-volatile and volatile compounds from 'microwave and roasting bags' (MRB), made of Nylon 6,6 (and some Nylon 6), into chicken meat, skin, and juices during roasting (200 degrees C/2 h) in a conventional oven was determined. For measurement of migration of non-volatile compounds, cooked chicken was freeze-dried, extracted with methanol after addition of 2-azacyclononane (internal standard) and the extract cleaned-up using liquid-solid adsorption chromatography (silica gel). High performance liquid chromatography (HPLC) in the reverse phase mode using a linear gradient of methanol in water was used to quantify seven Nylon 6 and Nylon 6,6 cyclic monomers and oligomers of molecular mass up to 678 daltons. Migration into chicken was 7.48 micrograms/g (8.26 mg/bag; 3.94 micrograms/cm2), 16% of the total non-volatile compounds contained in the MRB material. Individual migrants were also quantified. Migration of one volatile compound, 2-cyclopentyl cyclopentanone, into the roast chicken parts was measured. Extraction with diethyl ether, using a modified Likens-Nickerson system of concurrent steam distillation-solvent extraction with an internal standard (cyclohexanone) was performed for 10 h. Gas chromatography/mass spectrometry (GC/MS) in the selected ion mode (SIM) was used for quantification. An average of 14.0 (+/- 4.36) micrograms/bag (or micrograms/chicken) migrated, being 0.08% of the total 2-cyclopentyl cyclopentanone present in MRB. Loss of volatile compounds to the atmosphere is believed to have occurred since there was another, more volatile compound (cyclopentanone), present in MRB, at levels higher than 2-cyclopentyl cyclopentanone, but this was not detected in roast chicken. In general, the transference of MRB components into roast chicken can be considered not to present a hazard.     

Predicting the effects of optical defocus on human contrast sensitivity

We used diffraction modulation transfer functions and model eyes to predict the effect of defocus on the contrast sensitivity function (CSF) and compared these predictions with previously published experimental data. Using the principle that optically induced changes in the modulation transfer function should be paralleled by identical changes in the CSF, we used the modulation transfer function calculations with the best-focus CSF measurements to predict the defocused CSF. An aberration-free model predicted the effects of defocus well when the CSF was measured with small pupils (e.g., 2 mm) but not with larger pupils (6-8 mm). When the model included average aberrations, prediction of the defocused CSF with large pupils was better but remained inaccurate, failing, in particular, to reflect differences between individual subjects. Inclusion of measured aberrations for individual subjects provided accurate predictions in the shape of the monochromatic CSF of two of three subjects with hyperopic defocus and good predictions of the polychromatic CSF of two subjects with hyperopic defocus. Prediction of the effects of myopic defocus by use of measured individual aberrations of one subject were less successful. Hence a diffraction optics model can provide good predictions of the effects of defocus on the human CSF, given that one has knowledge of the individual ocular aberrations. These predictions are dependent on the quality of the aberration measurements.     

Association between human immunodeficiency virus and herpes simplex virus type 2 seropositivity among male factory workers in Zimbabwe

To determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify correlates of infection, and to describe the correlation with human immunodeficiency virus (HIV) seropositivity, 224 HIV-negative and 191 HIV-positive male factory workers in Zimbabwe were screened for HSV-2-specific antibodies. HSV-2 seroprevalence was 35.7% among HIV-negative subjects and 82.7% among HIV-positive subjects. The weighted estimate of HSV-2 seroprevalence in this population is 44.6%. The correlation between HIV and HSV-2 remained significant after controlling for multiple sex partners, paying for sex, and history of sexually transmitted disease (adjusted odds ratio, 8.0; 95% confidence interval, 4.8-13.1). If the association between HSV-2 and HIV is causal, then the high seroprevalence of HIV and HSV-2 suggests that suppressive HSV-2 treatment should be considered as a strategy to reduce HIV transmission in this population. HSV-2 seroconversion may be a suitable surrogate end point to evaluate HIV prevention interventions.     

Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic

Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.     

ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy

OBJECTIVES: Beta2-integrin (CD11b/CD18) expression, an indicator of neutrophil activation, has been associated with the development of acute respiratory distress syndrome. Leumedins act directly on leukocytes to inhibit the up-regulated expression of beta2-integrins involved in leukocyte adhesion. We examined the effect of such a new anti-inflammatory agent, NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl]-L-leucine), on neutrophil-mediated acute lung injury in an animal model. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Adult New Zealand rabbits. INTERVENTIONS: After repeated lung lavages with normal saline to induce acute lung injury, anesthetized rabbits were randomly assigned to one of two groups (n = 6 per group): a) treatment group (pretreated with NPC 15669 [10 mg/kg i.v. bolus] 30 mins before lavage, followed by a continuous infusion [5 mg/kg/hr] for the duration [4 hrs] of the experiment); or b) control group (pretreatment and continuous infusion with placebo). All animals were mechanically ventilated with identical pressure settings over 4 hrs and were killed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: PaO2, PaCO2, and tidal volumes were repeatedly measured and airway pressure settings were noted every 30 mins. At the end of the experiment, lungs were taken out for measurements of the myeloperoxidase content, for conventional histology (hematoxylin and eosin staining), and for intracellular adhesion molecule-1 immunohistostaining. Pretreatment with NPC 15669 profoundly improved oxygenation from a PaO2 of 52 +/- 5 torr (6.9 +/- 0.7 kPa) to 250 +/- 161 torr (33.3 +/- 21.5 kPa) within 60 mins after lung lavage (p < .05). Oxygenation continued to improve throughout the study, reaching a maximal PaO2 value of 395 +/- 98 torr (52.7 +/- 13.1 kPa) at 4 hrs. In the control group, oxygenation remained poor throughout the observation period. PaO2 values differed significantly (51 +/- 20 torr [6.8 +/- 2.7 kPa] vs. 306 +/- 126 torr [40.8 +/- 16.8 kPa], p < .005) at 90 mins and at all subsequent measurements from those values in the NPC 15669 group. Dynamic lung compliance improved significantly 60 to 90 mins after repeated lung lavage. Histology demonstrated markedly less lung damage (hyaline membrane formation and leukocyte infiltration) in treated animals (p < .05) than in controls. CONCLUSIONS: NPC 15669 seems to block inflammatory reactions by inhibiting the sequestration of neutrophils in acute, ventilator-associated lung injury. As a result, gas exchange and total lung compliance improve. Application of this and similar compounds affecting neutrophil adhesion warrants further investigation as a treatment modality for acute lung injury.     

Bacterial lipopolysaccharide can enter monocytes via two CD14-dependent pathways

Host recognition and disposal of LPS, an important Gram-negative bacterial signal molecule, may involve intracellular processes. We have therefore analyzed the initial pathways by which LPS, a natural ligand of glycosylphosphatidylinositol (GPI)-anchored CD14 (CD14-GPI), enters CD14-expressing THP-1 cells and normal human monocytes. Exposure of the cells to hypertonic medium obliterated coated pits and blocked 125I-labeled transferrin internalization, but failed to inhibit CD14-mediated internalization of [3H]LPS monomers or aggregates. Immunogold electron microscope analysis found that CD14-bound LPS moved principally into noncoated structures (mostly tubular invaginations, intracellular tubules, and vacuoles), whereas relatively little moved into coated pits and vesicles. When studied using two-color laser confocal microscopy, internalized Texas Red-LPS and BODIPY-transferrin were found in different locations and failed to overlap completely even after extended incubation. In contrast, in THP-1 cells that expressed CD14 fused to the transmembrane and cytosolic domains of the low-density lipoprotein receptor, a much larger fraction of the cell-associated LPS moved into coated pits and colocalized with intracellular transferrin. These results suggest that CD14 (GPI)-dependent internalization of LPS occurs predominantly via noncoated plasma membrane invaginations that direct LPS into vesicles that are distinct from transferrin-containing early endosomes. A smaller fraction of the LPS enters via coated pits. Aggregation, which greatly increases LPS internalization, accelerates its entry into the nonclathrin-mediated pathway.     

Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.