Community health workers: collaborating to support breastfeeding among high-risk inner-city mothers.

Background: Low breastfeeding rates persist as a health disparity among high-risk inner-city mothers. We sought to obtain input of community health workers (CHWs) in preparation for a breastfeeding intervention.

Subjects And Methods: We conducted audiotaped focus groups with CHWs of the Cleveland (OH) Department of Public Health's MomsFirst™, a federally funded Healthy Start program, which addressed interest in breastfeeding, positives and negatives of breastfeeding, perceived barriers, and an intervention concept.

The spectrum of polycystic kidney disease in children.

Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are important inherited kidney diseases with distinct clinical features and genetics. Although these diseases have classically been considered "adult" (ADPKD) or "infantile/pediatric" (ARPKD), it is now clear that both diseases can present in children and adults. ADPKD and ARPKD also share important pathophysiologic features, including cilia dysfunction.

The role of CD18 in the production and release of neutrophils from the bone marrow.

Neutrophil numbers must be tightly controlled to maintain host protection and prevent neutrophil-mediated tissue injury. CD18 deficiency leads to neutrophilia and myeloid hyperplasia in the bone marrow (BM). These studies examined the function of CD18 in regulating neutrophil production and determined whether the defects in neutrophil production that are observed in CD18 deficiency persist in the presence of wild-type (WT) leukocytes that confer host protection.

Changes in the hyperelastic properties of endothelial cells induced by tumor necrosis factor-alpha.

Mechanical properties of living cells can be determined using atomic force microscopy (AFM). In this study, a novel analysis was developed to determine the mechanical properties of adherent monolayers of pulmonary microvascular endothelial cells (ECs) using AFM and finite element modeling, which considers both the finite thickness of ECs and their nonlinear elastic properties, as well as the large strain induced by AFM. Comparison of this model with the more traditional Hertzian model, which assumes linear elastic behavior, small strains, and infinite cell thickness, suggests that the new analysis can predict the mechanical response of ECs during AFM indentation better than Hertz's model, especially when using force-displacement data obtained from large indentations (>100 nm).

Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV.

Background: Decreased bone mineral density (BMD) is prevalent in HIV-infected patients. Bisphosphonates are currently the mainstay of treatment for postmenopausal and male osteoporosis in HIV-uninfected individuals; however, their efficacy and safety in HIV-infected patients remains unclear.

Methods: In this prospective, randomized, placebo-controlled multicenter trial, we studied the effectiveness of calcium and vitamin D supplementation with or without alendronate in improving BMD in HIV-infected subjects receiving stable antiretroviral therapy.

Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis.

Objectives: To characterize the rate of decline of forced expiratory volume in 1 second (FEV(1)) in children and adolescents with cystic fibrosis and to identify and compare risk factors associated with FEV(1) decline.

Study Design: The rate of decline in FEV(1)% predicted over 3 to 6 years in 3 different age groups was determined. Risk factors for decline were identified and compared among and within age groups as a function of disease severity with repeated-measures, mixed-model regression.

Neutrophils in innate immunity.

Neutrophils are an important component of innate immunity in the lungs. During bacterial pneumonia, neutrophils are recruited from the capillaries of the pulmonary circulation in the gas-exchanging regions of the lungs. This process requires the coordinated activation of many cells within the lungs, including neutrophils and capillary endothelial cells.

Interleukin 10 extends the effectiveness of standard therapy during late sepsis with serum interleukin 6 levels predicting outcome.

Patients with septic shock often display features of T cell hyporesponsiveness and immune suppression, which, if persistent, are associated with increased mortality. In the murine cecal ligation and puncture (CLP) model of sepsis, we previously reported that early treatment with the anti-inflammatory cytokine interleukin 10 (IL-10) delays the onset of irreversible shock, defined as the time at which rescue surgery to remove the necrotic cecum is no longer effective. Because IL-10 can be immunostimulatory for T cells, we hypothesized that in the CLP model, late IL-10 treatment after removal of the infectious nidus at the onset of irreversible shock would restore T cell responsiveness and increase survival.

Transforming growth factor alpha (TGF-alpha) and other targets of tumor necrosis factor-alpha converting enzyme (TACE) in murine polycystic kidney disease.

Transforming growth factor-alpha (TGF-alpha) is abnormally expressed in autosomal recessive polycystic kidney disease (ARPKD). Tumor necrosis factor-alpha converting enzyme (TACE), a metalloproteinase, mediates TGF-alpha processing. In this study, we sought to determine whether TGF-alpha was an absolute requirement for renal cystogenesis and whether its absence would modulate disease severity or related growth factors/receptors expression.

Association of observed family relationship quality and problem-solving skills with treatment adherence in older children and adolescents with cystic fibrosis.

Objective: To examine associations between observations of the quality of family relationships and problem-solving skills and reported adherence to medical treatments for older children and adolescents with cystic fibrosis (CF).

Methods: Reports of adherence were obtained from 96 youth with CF and their parents recruited from six CF centers in the Midwest and southeastern United States. Videotaped observations of family discussions of high conflict issues were used to assess quality of relationships and problem-solving skills.

EGF-related growth factors in the pathogenesis of murine ARPKD.

Background: Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and their receptor, EGFR, play key roles in polycystic kidney disease (PKD) pathogenesis. Renal expression of two related growth factors, amphiregulin and heparin-binding EGF, has not been examined previously in PKD. The aims of this study of murine autosomal-recessive polycystic kidney disease (ARPKD) were (1) to characterize amphiregulin and heparin-binding EGF expression in cystic versus normal kidneys and cells; and (2) to identify the functional effects of abnormal EGF-related growth factor expression.

How do primary care physicians manage children with possible developmental delays? A national survey with an experimental design.

Objective: Although early detection and treatment of developmental delays can improve outcome, little is known about factors that influence how primary care physicians manage young children with probable developmental delays. The objective of this study was to describe physician referral practices for children with developmental delays and to test whether the probability of referral is increased by 1) the expression of parental concern; 2) female gender in a child with language delay; 3) disruptive, as opposed to avoidant behaviors; and 4) physician characteristics, including female gender or being a pediatrician.

Methods: A cross-sectional survey was mailed to a national random sample of 800 pediatricians and 800 family practice physicians in primary care practice, using an experimental randomized block design.

Activation of SRC tyrosine kinases in response to ICAM-1 ligation in pulmonary microvascular endothelial cells.

Previous studies demonstrated that ICAM-1 ligation on human pulmonary microvascular endothelial cells (ECs) sequentially induces activation of xanthine oxidase and p38 MAPK. Inhibition of these signaling events reduces neutrophil migration to the EC borders. This study examined the role of SRC tyrosine kinases in ICAM-1-initiated signaling within these ECs.

Accelerated intravenous rehydration.

To determine whether accelerated intravenous (i.v.) rehydration using a new Isotonic Dehydration Worksheet results in: (1) complications in serum sodium or volume status, and (2) decreased duration of i.

Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis.

Objective: To determine the relation of growth and nutritional status to pulmonary function in young children with cystic fibrosis (CF).

Study Design: The relation of weight-for-age (WFA), height-for-age (HFA), percent ideal body weight (%IBW), and signs of lung disease at age 3 years with pulmonary function at age 6 years was assessed in 931 patients with CF. Associations of changes in WFA from age 3 to 6 on pulmonary function were also assessed.

Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation.

Neutrophil adherence to tumor necrosis factor-alpha (TNF-alpha)-treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)-dependent signaling events. This study determined whether similar changes occurred in rat PMECs and whether rat pulmonary arterial endothelial cells (PAECs) responded differently. Neutrophil adherence induced an increase in the formation of F-actin and in the apparent stiffness of TNF-alpha-treated rat PMECs.

Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice.

This study tested the hypothesis that very late antigen (VLA)-4 mediates CD18-independent neutrophil emigration into the airspaces induced by either Streptococcus pneumoniae, a stimulus that induces primarily CD18-independent neutrophil emigration, or Escherichia coli, toward which only 20-30% of the total number of neutrophils emigrate through CD18-independent pathways. In wild-type (WT) mice, VLA-4 expression was less on neutrophils that emigrated into the airspaces than on circulating neutrophils. Vascular cell adhesion molecule-1 (VCAM-1) mRNA, the major endothelial cell ligand for VLA-4, increased more in E.

Phenotypic analysis of conditionally immortalized cells isolated from the BPK model of ARPKD.

To study the pathophysiology of autosomal recessive polycystic kidney disease (ARPKD), we sought to develop conditionally immortalized control and cystic murine collecting tubule (CT) cell lines. CT cells were isolated from intercross breedings between BPK mice (bpk(+/-)), a murine model of ARPKD, and the Immorto mice (H-2K(b)-ts-A58(+/+)). Second-generation outbred offspring (BPK x Immorto) homozygous for the BPK mutation (bpk(-/-); Im(+/+/-); cystic BPK/H-2K(b)-ts-A58), were phenotypically indistinguishable from inbred cystic BPK animals (bpk(-/-)).

A novel inhibitor of tumor necrosis factor-alpha converting enzyme ameliorates polycystic kidney disease.

Background: Transforming growth factor-alpha (TGF-alpha) expression is abnormal in polycystic kidney disease. We previously demonstrated that blockade of the epidermal growth factor receptor (EGFR), the receptor for TGF-alpha, significantly slowed disease progression in the bpk murine model of autosomal-recessive kidney disease (ARPKD). In the present study, kidney TGF-alpha expression in this model is characterized, and the therapeutic potential of inhibiting TGF-alpha in ARPKD is examined using a novel inhibitor of tumor necrosis factor-alpha converting enzyme (TACE), the metalloproteinase that cleaves membrane-bound TGF-alpha to release the secreted ligand.

Autonomic abnormalities in children with functional abdominal pain: coincidence or etiology?

Background: There is increasing evidence that autonomic neuropathies may adversely affect gastrointestinal motility by involving the extrinsic nerves of the gut. The authors' hypothesize that functional abdominal pain in children is associated with generalized autonomic dysfunction.

Methods: The authors performed detailed autonomic testing in eight patients with functional abdominal pain, including deep breathing, Valsalva, tilting (to assess parasympathetic and sympathetic adrenergic function), and axon-reflex function and thermoregulatory sweat testing to assess sympathetic cholinergic function.

Role of CFTR in autosomal recessive polycystic kidney disease.

An extensive body of in vitro data implicates epithelial chloride secretion, mediated through cystic fibrosis transmembrane conductance regulator (CFTR) protein, in generating or maintaining fluid filled cysts in MDCK cells and in human autosomal dominant polycystic kidney disease (ADPKD). In contrast, few studies have addressed the pathophysiology of fluid secretion in cyst formation and enlargement in autosomal recessive polycystic kidney disease (ARPKD). Murine models of targeted disruptions or deletions of specific genes have created opportunities to examine the role of individual gene products in normal development and/or disease pathophysiology.

Segment-specific c-ErbB2 expression in human autosomal recessive polycystic kidney disease.

c-ErbB2 (also referred to as Neu or HER2), a transmembrane glycoprotein with intrinsic tyrosine kinase activity, is structurally related to epidermal growth factor receptor (EGFR) and forms active heterodimers with EGFR as well as other members of the EGFR family. c-ErbB2 is reported to mediate differentiation and proliferation in epithelial cells and is expressed in a tissue-specific and developmental stage-specific manner. Given the role of EGFR in cystic renal epithelial hyperplasia and the immature phenotype of cystic renal epithelial cells, the segment-specific expression pattern of c-ErbB2 in human autosomal recessive polycystic kidney disease (ARPKD) was examined in nine ARPKD kidney specimens ranging from gestational age 17 wk through postnatal age 4 wk.