Temporal trends and predictors of gestational exposure to organophosphate ester flame retardants and plasticizers.

BACKGROUND: Organophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal trends and predictors of OPE exposure are primarily limited by small sample sizes. OBJECTIVES: Characterize temporal trends and predictors of OPE exposure biomarkers. METHODS: We determined urinary concentrations of eight biomarkers of OPE exposure at three timepoints during pregnancy for participants in the LIFECODES Fetal Growth Study (n = 900), a nested case-cohort recruited between 2007 and 2018. We examined biomarker concentrations, their variability during pregnancy, and temporal trends over the study period. In addition, we identified sociodemographic and pregnancy characteristics associated with biomarker concentrations. Analyses were conducted using both the within-subject pregnancy geometric means and biomarker concentrations measured at individual study visits. RESULTS: Five OPE biomarkers were detected in at least 60% of the study participants. Biomarkers were not strongly correlated with one another and intraclass correlation coefficients, measuring within-subject variability during pregnancy, ranged from 0.27 to 0.51. Biomarkers exhibited varying temporal trends across study years. For example, bis(1-chloro-2-propyl) phosphate (BCIPP) increased monotonically, whereas bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), displayed non-monotonic trends with concentrations that peaked between 2011 and 2014. We observed associations between sociodemographic characteristics and OPE biomarkers. In general, concentrations of most OPE biomarkers were higher among participants from racial and ethnic minority populations, participants who were younger, had higher pre-pregnancy body mass index (BMI), and less than a college degree. We observed consistent results using either averaged or visit-specific biomarker concentrations. SIGNIFICANCE: We observed widespread exposure to several OPEs and OPE biomarkers displayed varying temporal trends in pregnant people from 2007 to 2018. Concentrations of most OPE biomarkers varied according to sociodemographic factors, suggesting higher burdens of exposure among participants with higher pre-pregnancy BMI, those belonging to racial and ethnic minority populations, and lower educational attainment.

Temporal trends and predictors of phthalate, phthalate replacement, and phenol biomarkers in the LIFECODES Fetal Growth Study.

BACKGROUND: Exposure to many phthalates and phenols is declining as replacements are introduced. There is little information on temporal trends or predictors of exposure to these newer compounds, such as phthalate replacements, especially among pregnant populations. OBJECTIVE: Examine temporal trends and predictors of exposure to phthalates, phthalate replacements, and phenols using single- and multi-pollutant approaches. METHODS: We analyzed data from 900 singleton pregnancies in the LIFECODES Fetal Growth Study, a nested case-cohort with recruitment from 2007 to 2018. We measured and averaged concentrations of 12 phthalate metabolites, four phthalate replacement metabolites, and 12 phenols in urine at three timepoints during pregnancy. We visualized and analyzed temporal trends and predictors of biomarker concentrations. To examine chemical mixtures, we derived clusters of individuals with shared exposure profiles using a finite mixture model and examined temporal trends and predictors of cluster assignment. RESULTS: Exposure to phthalates and most phenols declined across the study period, while exposure to phthalate replacements (i.e., di(isononyl) cyclohexane-1,2-dicarboxylic acid, diisononyl ester [DINCH] and di-2-ethylhexyl terephthalate [DEHTP]) and bisphenol S (BPS) increased. For example, the sum of DEHTP biomarkers increased multiple orders of magnitude, with an average concentration of 0.92 ng/mL from 2007 to 2008 and 61.9 ng/mL in 2017-2018. Biomarkers of most chemical exposures varied across sociodemographic characteristics, with the highest concentrations observed in non-Hispanic Black or Hispanic participants relative to non-Hispanic White participants. We identified five clusters with shared exposure profiles and observed temporal trends in cluster membership. For example, at the end of the study period, a cluster characterized by high exposure to phthalate replacements was the most prevalent. SIGNIFICANCE: In a large and well-characterized pregnancy cohort, we observed exposure to phthalate replacements and BPS increased over time while exposure to phthalates and other phenols decreased. Our results highlight the changing nature of exposure to consumer product chemical mixtures.

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery.

BACKGROUND: While fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant [OPE] metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births. METHODS: This case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class. RESULTS: Among the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA (OR: 0.40 [95% CI: 0.18, 0.87]). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 [95% CI: 0.27, 0.89]) and phthalate metabolite concentrations (OR: 0.23 [95% CI: 0.07, 0.73]). Associations between consumer product chemicals and SGA were largely null. CONCLUSIONS: Joint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.

The current status of thermal ablation in the management of T1b renal masses.

The role of thermal ablation in the management of T1b renal masses is not well defined. The purpose of this review is to examine current evidence for cryoablation, radiofrequency ablation, and microwave ablation of T1b renal masses as well as review current AUA and EAU guidelines for thermal ablation of T1b masses. Given the size of these tumors, adjunctive maneuvers are often necessary to ensure patient safety and protect vital adjacent structures.

A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma.

PURPOSE: Mesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma. MATERIALS AND METHODS: Retrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)]. RESULTS: Percutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract. CONCLUSION: Percutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

Evaluation of infectious complications following percutaneous liver ablation in patients with bilioenteric anastomoses.

PURPOSE: Prior bilioenteric anastomosis (BEA) has been associated with elevated risk of abscess formation after thermal ablation of hepatic tumors. We assessed the incidence of hepatic abscess after thermal ablation in a BEA cohort treated with extended antibiotic regimens following ablation. MATERIALS AND METHODS: Retrospective review was performed to identify patients with BEA who underwent percutaneous hepatic thermal ablation between January 1, 2003-September 1, 2016. Fifteen patients with BEA underwent 18 percutaneous thermal ablation procedures. Patient and procedural characteristics were reviewed, as well as the antibiotic regiment utilized post ablation. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE) v4.03]. RESULTS: Fifteen patients with BEA underwent treatment of 49 liver lesions during 18 ablation sessions. Mean follow-up in these patients was 39 months (range 3-138 months). Two patients (11%) developed hepatic abscesses, both of which occurred within 45 days of the ablation procedure while the patients were still on extended prophylactic antibiotic therapy. No additional CTCAE clinically significant complications were observed. CONCLUSION: Thermal ablation of hepatic tumors can be accomplished safely in patients with BEA. Long-term post-procedural antibiotics may mitigate the risk of hepatic abscess formation. Due to the high number of patients who are deemed surgically unresectable, patients with BEA may have limited alternate treatment modalities and percutaneous hepatic thermal ablative treatments warrant consideration.

Contribution of whole platelet aggregometry to the endovascular management of unruptured aneurysms: an institutional experience.

BACKGROUND: Stent-assisted coiling of intracranial aneurysms is an efficient alternative treatment to surgical clipping but requires prolonged antiplatelet therapy. Some patients are non-responsive to aspirin and/or clopidogrel. OBJECTIVE: To analyze the implications of this assessment using the 'whole blood aggregometry (WBA) by impedance' technique. MATERIALS AND METHODS: The Southwestern Tertiary Aneurysm Registry was reviewed between 2002 and 2012 for patients with unruptured aneurysms treated with stent-assisted coiling. The study population was divided into patients who were tested preoperatively for platelet responsiveness to aspirin and clopidogrel ('tested' patients) and those who were not ('non-tested'). Where necessary, tested patients received additional doses of antiplatelet drugs to achieve adequate platelet inhibition. Endpoints included the incidence of non-responsiveness, the rates of thrombotic and hemorrhagic complications, and the rates of permanent morbidity and mortality. RESULTS: A total of 266 patients fulfilled our selection criteria: 114 non-tested patients who underwent 121 procedures, and 152 tested patients who underwent 171 procedures. The two groups did not vary significantly in patient age, gender, and aneurysms location. Aspirin non-responsiveness was detected in 3 patients (1.75%) and clopidogrel non-responsiveness in 21 patients (12.3%). Non-tested patients had an 11.6% rate of thrombotic complications with a 4.1% permanent morbidity or mortality rate versus 2.3% and 0.6% in tested patients (p=0.0013). The incidence of hemorrhagic complications was similar between the two groups. CONCLUSIONS: Preoperative platelet inhibition testing using WBA can be useful to assess and correct antiaggregant non-responsiveness, and may reduce postoperative mortality and permanent morbidity.

Auto-brewery Syndrome in the Setting of Long-standing Crohn's Disease: A Case Report and Review of the Literature.

CLINICAL BACKGROUND: A 71-year-old male with 50-year history of Crohn's disease was evaluated for acute onset of dizziness and slurred speech. Blood ethanol levels were elevated despite abstinence from alcohol for over 30 years. CT enterography demonstrated massive dilation of the small bowel with anastomotic stricture. DISCUSSION: Auto-brewery syndrome may be considered in a patient with chronic obstruction or hypomotility presenting with elevated serum ethanol levels in the setting of high carbohydrate intake. Although treatment algorithms lack validation, judicious use of antibiotic therapy, carbohydrate control, and short courses of antifungal therapy have all been reported in the literature. Importantly, clinical consideration of 'auto-brewery' should be undertaken with substantial caution, given the lack of validated mechanisms linking endogenous ethanol production to peripheral blood ethanol.

A multicentre randomized trial of the treatment of patients with pemphigus vulgaris with infliximab and prednisone compared with prednisone alone.

BACKGROUND: Pemphigus vulgaris (PV) is a blistering disease and tumour necrosis factor-α has a role in its pathogenesis. OBJECTIVES: To evaluate the safety of infliximab (IFX) with prednisone compared with prednisone alone in the treatment of PV. In addition, treatment response was assessed and mechanistic studies were performed. METHODS: Subjects with PV who had ongoing disease activity while being maintained on prednisone were randomized to receive either IFX or placebo in addition to prednisone. Response status and immunoglobulin (Ig) G anti-desmoglein (Dsg)1 and Dsg3 antibodies were assessed at 18 and 26 weeks. RESULTS: Ten subjects were randomized to each group. There were no safety signals during the course of the study. At week 18, one subject in each group had responded. At week 26, three IFX-treated subjects vs. none in the placebo group had responded (P = 0·21). At weeks 18 and 26, the median IgG anti-Dsg1 and anti-Dsg3 levels were lower in the IFX-treated patients [IgG anti-Dsg-1 (week 18, P = 0·035; week 26, P = 0·022); IgG anti-Dsg3 (week 18, P = 0·035; week, 26 P = 0·05)]. CONCLUSIONS: This study is limited by the relatively small sample size. There was no significant difference between study arms in the proportion of subjects with treatment-related adverse events > grade 3. IFX therapy was not shown to be effective for the treatment of patients with PV in this randomized, placebo-controlled trial, although IFX treatment may be associated with a decrease in anti-Dsg1 and Dsg3 antibodies.

Brainstem melanomas presenting as a cavernous malformation.

BACKGROUND: Melanoma lesions in the brainstem can be difficult to distinguish radiographically and clinically from cavernous malformations. However, the treatment modalities and clinical course of these two diseases differ considerably. We report two cases of melanoma presenting as brainstem hemorrhages. CASE DESCRIPTION: A 69-year-old male was found to have a hemorrhagic lesion of the right dorsal midbrain. After a repeat hemorrhage, the lesion was resected and found to be hyperchromatic. Nonetheless, the patient suffered rebleeding and died 3 months later. A 62-year-old female was similarly found to have an acute pontine hemorrhage. After resection of the lesion, she underwent whole-brain radiation therapy but ultimately died 5.5 months later. The histopathology of both lesions was consistent with melanoma. CONCLUSIONS: Melanoma in the brainstem can mimic cavernous malformations. While management of these lesions includes stereotactic radiosurgery, whole-brain radiation, and surgical resection, metastatic brainstem melanoma follows an aggressive clinical course with a poor prognosis.

Dark-field microscopy in the assessment of large colon microperfusion and mucosal injury in naturally occurring surgical disease of the equine large colon.

REASON FOR PERFORMING STUDY: Intraoperative assessment of colonic viability can be challenging and largely subjective. Objective methods are often impractical. Viability is related to re-establishment of colonic perfusion; particularly microvascular perfusion. This study evaluated the utility of dark-field microscopy (DFM) of the colonic serosa as an objective method of assessing microperfusion. OBJECTIVES: To measure microvascular perfusion indices (MPI) of the pelvic flexure serosa in horses with surgical colonic lesions and correlate these with macroperfusion indices (MaPI) and histomorphometry. STUDY DESIGN: Prospective, clinical, case-control study. METHODS: Control horses and horses with colonic volvulus (LCV), displacement, and/or simple obstruction undergoing surgery had DFM video loops performed on the pelvic flexure. Total vessel density, perfused vessel density, proportion of perfusion vessels and microvascular flow index were calculated from video analysis. Macroperfusion indices (arterial blood pressure and heart rate) were recorded. Histomorphometry was used to determine a mucosal injury score. Differences between lesions for MPI, MaPI and histomorphometry were compared using ANOVA or Kruskal-Wallis statistic. Spearman correlations between MPI with MaPI were performed. Linear regression was used to assess the relationship between MPI and histomorphometry. P<0.05 was significant. RESULTS: Horses with LCV had lower perfused vessel density, proportion of microvascular perfusion vessels and flow index than horses with nonstrangulating obstructions and control horses. Macroperfusion indices were not correlated with MPI but MPI were correlated with histomorphometry. CONCLUSIONS: Dark-field microscopy is achievable in the operating room and can quantify MPI from the colonic serosa in different colonic lesions. Macroperfusion indices were not related with colonic MPI. Microvascular perfusion indices can predict the severity of histopathological change at the pelvic flexure. Derangements of MPI may be more useful indicators of colonic pathology and viability and offer a more objective assessment of intestinal injury than subjective methods. Further study is needed to determine the utility of DFM in predicting survival in horses with LCV.

Preoperative embolization of cerebral arteriovenous malformations with onyx.

BACKGROUND AND PURPOSE: Preoperative embolization facilitates the surgical management of complex cerebral arteriovenous malformations (cAVMs). This analysis aims to investigate the risks for preoperative cAVM embolization with Onyx. MATERIALS AND METHODS: We retrospectively analyzed clinical data of all patients who underwent embolization with Onyx as a preoperative treatment of cAVMs at our institution since 2005 (US Food and Drug Administration [FDA] approval). Patients with arteriovenous fistulas were excluded. A total of 107 patients were treated for cAVMs during the study period. Of those patients, 41 underwent cAVM embolizations with Onyx in 82 procedures. RESULTS: After the embolization, the cAVM diameter was reduced from 3.71 +/- 1.55 cm to 3.06 +/- 1.89 cm (P < .05). Median volume reduction was 75%. Complete occlusion with embolization alone was achieved in 4 (10%) cAVMs. The recurrence rate for completely occluded cAVMs was 50% (2 patients). A total of 71% of the 41 patients treated with Onyx underwent surgery, and 15% underwent radiosurgery. There were 9% who have not yet received definitive treatment of their residual cAVMs. A new permanent neurologic deficit occurred in 5 patients (6.1% per procedure or 12.2% per patient). CONCLUSIONS: A considerable risk for a permanent neurologic deficit remains for cAVM embolization with Onyx. The risk has to be carefully weighted against the benefit of volume reduction in the treatment of cAVMs.

Retrograde crossing stent placement strategies at the basilar apex for the treatment of wide necked aneurysms: reconstructive and deconstructive opportunities.

Neck remodeling devices such as the Neuroform or Enterprise greatly facilitate the endovascular treatment of wide necked basilar apex aneurysms. The complex anatomy of the basilar apex affords opportunity for antegrade, multiple crossing and retrograde device placement strategies to facilitate coil embolization. A retrograde approach is possible in the presence of a posterior communicating artery large enough to allow device navigation. Our experience with a retrograde device placement strategy in three patients is reported. In two patients, device positioning extended from one P1 segment of the posterior cerebral artery to the other across the basilar apex. In one patient, device positioning extended from the P1 segment of the posterior cerebral artery across the basilar apex into the opposite superior cerebellar artery. All patients underwent reconstructive or deconstructive uncomplicated coil embolization after device placement with stable aneurysm occlusion on follow-up angiography. In appropriate anatomic situations, retrograde stent placement across the basilar apex through a posterior communicating artery may represent a preferred strategy for wide necked basilar apex aneurysms.

Influence of patient age and stenosis location on wingspan in-stent restenosis.

BACKGROUND AND PURPOSE: Wingspan is a self-expanding, microcatheter-delivered microstent specifically designed for the treatment of symptomatic intracranial atherosclerotic disease. Our aim was to discuss the effect of patient age and lesion location on in-stent restenosis (ISR) rates after percutaneous transluminal angioplasty and stenting (PTAS) with the Wingspan system. MATERIALS AND METHODS: Clinical and angiographic follow-up results were recorded for all patients from 5 participating institutions. ISR was defined as >50% stenosis within or immediately adjacent (within 5 mm) to the implanted stent and >20% absolute luminal loss. For the present analysis, patients were stratified into younger (55 years) age groups. RESULTS: ISR occurred at a rate of 45.2% (14/31) in the younger group and 24.2% (15/62) in the older group (odds ratio, 2.6; 95% confidence interval, 1.03-6.5). In the younger group, ISR occurred after treatment of 13/26 (50%) anterior circulation lesions versus only 1/5 (20%) posterior circulation lesions. In the older group, ISR occurred in 9/29 (31.0%) anterior circulation lesions and 6/33 (18.2%) posterior circulation lesions. In young patients, internal carotid artery lesions (10/17 treated, 58.8%), especially those involving the supraclinoid segment (8/9, 88.9%), were very prone to ISR. When patients of all ages were considered, supraclinoid segment lesions had much higher rates of both ISR (66.6% versus 24.4%) and symptomatic ISR (40% versus 3.9%) in comparison with all other locations. CONCLUSION: Post-Wingspan ISR is more common in younger patients. This increased risk can be accounted for by a high prevalence of anterior circulation lesions in this population, specifically those affecting the supraclinoid segment, which are much more prone to ISR and symptomatic ISR than all other lesions.

Phantom evaluations of a dedicated dual-head scintimammography system.

Results of aboratory evaluations are presented of the dual-head scintimammography system using two opposed and co-registered compact gamma heads. The system is intended for clinical studies imaging suspicious lesions in a compressed breast. The studies were performed using 5 cm and 6 cm compressed breast phantoms with lesion sizes from 6 to 10 mm and lesion to breast tissue activity ratios from 6 to 10. Two imagers with a field-of-view (FOV) of 15 cmx20 cm were placed on the opposite sides of the breast phartoms. In some studies anthropomorphic torso phantom was used to simulate realistic scatter gamma radiation field. Two types of parallel-hole lead collimators were employed. Combining the co-registered images from both detector heads resulted in an over two-fold increase in lesioin contrast in the central plane of the phantom and substantially increased detection sensitivity over the whole breast volume, especially of asymmetrically placed small lesions. The results confirm the important advantage of a co-registoed two-head scintimammography system over a single head system in lesion detection and localization.

Inguinal cord cysts.

Inguinal cord cysts are found in less than 1% of inguinal hernia dissections. They are benign masses anatomically distinct from scrotal hydroceles that frequently mimic incarcerations or may have unusual tissue components; therefore it is recommended that they be removed when encountered to prevent future symptoms. Five cases of male inguinal cord cysts treated by the same surgeon are reviewed.

Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.

Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.