Histopathologic studies of the liver following intravenous colloidal 198Au therapy

Histologic studies of liver tissue from 27 patients given up to 395 mCi (cumulative) of intravenous colloidal 198Au showed no definite radiation injury and no correlation between hepatic abnormalities and dose. Demonstration of aggregates of colloidal gold in the Kupffer cells was inconsistent, suggesting slow removal or dispersion. Although the liver ordinarily receives the highest radiation dose, the critical organ is the marrow. Results support the recent introduction of 198Au to supplement teletherapy for certain neoplasms diffusely infiltrating the liver. Apparently the beta distribution minimizes endothelial injury in large vessels, which has been shown to be the cause of radiation hepatitis.     

Effect of antibiotics on polymorphonuclear neutrophil apoptosis

STUDY OBJECTIVE: To evaluate the effects of various antibiotics-direct and indirect as a result of bacterial killing-on polymorphonuclear neutrophil (PMN) apoptosis. DESIGN: In vitro analysis. SETTING: Research laboratory. INTERVENTION: Whole blood collected from healthy human subjects was incubated with and without Klebsiella pneumoniae (1.0 x 10(5) colony-forming units [cfu]/ml) plus ceftazidime 50 microg/ml, gentamicin, ciprofloxacin, trovafloxacin, tetracycline, doxycycline, erythromycin, azithromycin (each 5 microg/ml), or lipopolysaccharide 10 microg/ml. After staining with fluorescein-conjugated annexin V, red blood cells were lysed, and the remaining white blood cells were assessed by flow cytometry with gating on PMNs. MEASUREMENTS AND MAIN RESULTS: In the absence of K. pneumoniae infection, antibiotic exposure directly decreased PMN apoptosis by 17.8% (range -25.0% to -13.9%, p=0.008) compared with untreated cells. In the presence of K. pneumoniae, all antibiotic treatments, even those with poor in vitro activity for the bacterial isolate, decreased PMN apoptosis by 26.2% (range -38.0% to -17.8%, p<0.001) compared with untreated control cells and by 36.6% compared with untreated (no antibiotic) K. pneumoniae-stimulated cells (range -46.2% to -28.0%, p<0.001). CONCLUSIONS: All tested antibiotics in clinically relevant concentrations resulted in modest yet consistent decreases in PMN apoptosis. The magnitude of this change increased slightly in the presence of K. pneumoniae infection. In vivo studies are needed to determine whether antibiotic-associated prolongation of PMN survival improves host response to infection.     

Population control of resident and immigrant microglia by mitosis and apoptosis

Microglial population expansion occurs in response to neural damage via processes that involve mitosis and immigration of bone marrow-derived cells. However, little is known of the mechanisms that regulate clearance of reactive microglia, when microgliosis diminishes days to weeks later. We have investigated the mechanisms of microglial population control in a well-defined model of reactive microgliosis in the mouse dentate gyrus after perforant pathway axonal lesion. Unbiased stereological methods and flow cytometry demonstrate significant lesion-induced increases in microglial numbers. Reactive microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations.     

Microglial recruitment, activation, and proliferation in response to primary demyelination

We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45(dim)) using flow cytometry. Their expansion occurred rapidly and substantially outnumbered infiltrating macrophages and T cells throughout the course of cuprizone treatment. We used bromodeoxyuridine incorporation and bone marrow chimeras to show that both proliferation and immigration from blood accounted for increased microglial numbers. Microglia adopted an activated phenotype during demyelination, up-regulating major histocompatibility class I and B7.2/CD86. A subpopulation of CD45(dim-high) microglia that expressed reduced levels of CD11b emerged during demyelination. These microglia expressed CD11c and were potent antigen-presenting cells in vitro. T cells were recruited to the demyelinated corpus callosum but did not appear to be activated. Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate into demyelinated areas.     

Media and Young Minds: Comparing State Screen Media Use Regulations for Children Under 24 Months of Age in Early Care and Education to a National Standard

Introduction Excessive screen media use has been associated with a number of negative health outcomes in young children, including increased risk for obesity and comparatively lagging cognitive development. The purpose of this study was to assess state licensing regulations restricting screen media use for children under 24 months old in early care and education (ECE) and to compare regulations to a national standard. Methods We reviewed screen media use regulations for all US states for child care centers (“centers”) and family child care homes (“homes”) and compared these regulations to a national standard discouraging screen media use in children under 24 months of age. We assessed associations between state geographic region and year of last update with the presence of regulations consistent with the standard. In centers, 24 states had regulations limiting screen media use for children under 24 months of age and 19 states had regulations limiting screen media use in homes. Results More states in the South and fewer states in the Midwest had regulations limiting screen media use. The association between geographic region and regulations was not significant for centers (p?=?0.06), but was for homes (p?=?0.04). The year of last update (within the past 5 years versus older than 5 years) was not associated with regulations for centers (p?=?0.18) or homes (p?=?0.90). Discussion Many states lacked screen media use regulations for ECE. States should consider adding screen media use restrictions for children under 24 months based on current research data and current recommendations in future regulations updates.     

Evaluation of some anthropometric indices for the diagnosis of obesity in pregnancy in Nigeria: a cross-sectional study

Background

Obesity in pregnancy is a global health problem which is associated with poor pregnancy outcomes. The use of weight and height, measured at about ten weeks of gestation, to produce pre-gestational body mass index is recommended for the diagnoses of the condition but limitations abound in under resourced settings.

Objectives

To measure anthropometric indices such as mid upper arm circumference, calf circumference, waist circumference and waist to hip ratio, for identification of obesity in pregnancy.

Methods

Anthropometric measurements were carried out on cohorts of pregnant women from 4 hospitals in Enugu, South-eastern Nigeria.

Results

There were no significant difference in the mean mid upper arm circumference (MUAC) and calf circumference (CC) across the trimester groups. The mean values of waist circumferences, hip circumference and waist to hip ratios changed significantly across the trimesters. The 75^th percentile of MUAC (33 cm) and CC (39 cm) in all trimesters, had sensitivity and specificity of more than 70% for identifying obesity in pregnancy.

Conclusion

MUAC and CC values of 33cm and 39cm respectively might be reliable cut off points for diagnoses of obesity throughout pregnancy in Enugu, Nigeria     

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin''s lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC₅₀ values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.     

Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship

European Journal of Clinical Microbiology & Infectious Diseases - Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was...     

Evaluating sleep and sleep disorders in the pediatric primary care setting

Sleep is a vital physiologic function. Asking parents about their children's sleep should be part of every routine physical examination. Evaluating infants requires an understanding of changes in sleep associated with developmental stage. Problems with sleep associations may begin in late infancy and become a major issue for toddlers. Good sleep is crucial for success in learning for all children. Daytime behaviors in children may be symptoms of nighttime problems. Adolescents are often chronically sleep-deprived. Educating parents and their children about the importance of sleep is an important intervention that over time can help children lead happier, more productive lives.