Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion

The effect of flow on the adhesion of polymorphonuclear leukocytes (PMNL) to vascular endothelium was investigated using a parallel plate chamber with a well-defined flow field. Washed PMNL were perfused over a monolayer of primary human umbilical vein endothelial cells (HUVEC) pretreated with formyl-methionyl-leucyl-phenylalanine (FMLP, 1 X 10(-7) mol/L) for five minutes. In other experiments HUVEC were pretreated with interleukin 1 (IL1,2 U/mL) for four hours. PMNL adhesion to stimulated and control HUVEC was measured over a physiologic range of wall shear stresses. PMNL adhesion to nylon-coated surface was also studied. At a wall shear stress of 0.98 dynes/cm2,283 +/- 37.3 PMNL/mm2 (mean +/- SEM) adhered to FMLP-treated HUVEC while 195 +/- 20.3 PMNL/mm2 adhered to control HUVEC. At 1.96 dynes/cm2, 68 +/- 14.1 PMNL/mm2 adhered to FMLP-treated HUVEC and 42 +/- 6.0 PMNL/mm2 adhered to control HUVEC. At 3.92 dynes/cm2, virtually no PMNL adherence was noted on either control or FMLP-treated HUVEC. On IL 1-treated HUVEC at 1.96 dynes/cm2, 371 +/- 25.8 PMNL/mm2 adhered while 28 +/- 2.9 PMNL/mm2 adhered to control HUVEC. PMNL adhesion to IL 1-treated and control HUVEC dropped to 10.2 +/- 3.8 and 6.8 +/- 3.5 PMNL/mm2, respectively, at 3.01 dynes/cm2. The effect of flow on PMNL adhesion appears to be an important factor in determining the outcome of the PMNL/HUVEC adhesive interaction under these experimental conditions.     

Interleukin-1 alpha upregulates tumor necrosis factor receptors expressed by a human bone marrow stromal cell strain: implications for cytokine redundancy and synergy

To explore the biochemical and physiologic basis of the overlapping effects of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha) on myeloid cytokine production, we have studied the dynamics of granulocyte colony-stimulating factor (G-CSF) and granulocyte-monocyte colony-stimulating factor (GM-CSF) production as well as IL-1 receptor and TNF receptor expression in a clonally derived bone marrow stromal cell strain (CDCL). IL-1 alpha and TNF alpha act in a synergistic manner to stimulate G-CSF and GM-CSF production by CDCL, resulting in an increase in CSF secretion that is 250-fold greater than that observed with either cytokine alone. This synergism in protein secretion is paralleled by synergistic increases the steady-state level of GM- and G-CSF mRNA, with supra-additive levels achieved by 24 hours. Coincident with this synergistic induction of myeloid CSFs, treatment of CDCL cells with IL-1 alpha induces a 300% increase in the expression of TNF receptors. IL-1 alpha induction of TNF receptors reaches a peak after 6 hours and gradually returns to baseline level by 24 hours. IL-1 alpha does not affect TNF receptor ligand binding affinity. A kinetic study comparing IL-1/TNF synergistic induction of growth factor secretion with IL-1 alpha induction of TNF receptors shows that these events occur in parallel. In contrast with the induction of TNF receptors by IL-1 alpha, treatment with TNF alpha has no effect on either the number of IL-1 receptors expressed by CDCL cells or IL-1 receptor ligand binding affinity. Brief treatment of IL-1 alpha/TNF alpha-stimulated CDCL cells with cycloheximide before receptor induction reduces the synergistic increase in growth factor mRNA by 40% to 60% compared with cells not treated with CHX. Taken together, these results raise the possibility that IL-1 alpha cross-induction of TNF receptors may contribute to the biochemical mechanisms underlying the synergistic stimulation of G-CSF and GM-CSF production by IL-1 alpha and TNF alpha.     

The effect of culture-positive influenza type A on resource use and adverse events in nursing home residents

OBJECTIVES: To determine adverse clinical events and resource utilization associated with culture-positive influenza A in nursing home residents. DESIGN: A retrospective cohort study with cases and controls. SETTING: Seven hundred twenty-one-bed skilled nursing facility. PARTICIPANTS: One hundred fifty-four residents (21% of all residents) from whom influenza A was isolated during the 1997/98 season and matched controls. MEASUREMENTS: Baseline parameters, staff interventions, diagnostic tests, and adverse events were recorded from 60 days before to 60 days after specimen collection. The difference between each individual's before and after measurements determined excess utilization secondary to influenza. Controls were studied to determine time series effects. RESULTS: Baseline Minimum Data Set and nutritional parameters demonstrated significantly greater (P <.05) feeding dependency and lower serum albumin in the control group. Time series effects in the control group were negligible. Among cases, there were nine deaths within 30 days; among controls, there were four (chi2 P =.26). Within 30 days of onset, an average excess of 18 notations by nursing staff, one phone call to the physician, and one to family was noted per case. In half of cases, a nonscheduled physician visit was required. There was a 20% excess in physician orders for oxygen and bronchodilators. Chest x-rays were performed in half of the cases, and antibiotics were prescribed to half. Sixteen percent of cases had radiographic pneumonia, and 2% had congestive heart failure. The average cost for excess chest x-rays, laboratory services, antimicrobials, ambulance calls, hospital days, and emergency room and physician visits was $943.44. This does not include efforts by nursing home staff who accommodate functional decline on-site. CONCLUSION: An unexpected finding was that there were more impaired individuals who were less likely to have influenza detected or less likely to acquire influenza in the control group than in the influenza group. The morbidity, mortality, excess staff effort, and measured expenditure justify efforts to prevent influenza.     

Early assessment of the efficacy of digital infrared thermal imaging in pediatric extremity trauma

Young children or those with intellectual disability with trauma to an extremity often undergo radiographs of the whole limb. The objective of the study was to assess the efficacy of digital infrared thermal images (DITI) in pediatric extremity trauma. We hypothesized fractures to be associated with local hyperthermia, detectable with DITI, which could direct focused radiographs. In this exploratory study, patients seen over a 2-month period in a pediatric emergency department for limb trauma were included if an extremity radiograph was taken on the same day. Patients had DITI of symptomatic and contralateral limbs. The warmest area of each image was compared to the site of pain and/or fracture on the radiograph. Fifty-one patients were enrolled. DITI matched 73% of pain sites. Fractures were seen in 11 patients. DITI matched 7 of 11 (64%) fracture sites. DITI performance in pinpointing the site of injury, although suboptimal, is encouraging for further evaluation.     

Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles

The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of ultra high molecular weight polyethylene (UHMWPE) particles. Six groups of nude mice were used. We used non-invasive imaging to assay macrophage recruitment and osteolysis. A murine macrophage cell line and primary wild type and CCR2 knockout murine macrophages were used as the reporter cells. Particles were infused into the femoral canal. Bioluminescence and immunohistochemical staining were used to confirm the migration of reporter cells. Locally infused MCP-1 induced systemic macrophage trafficking to bone. Injection of MCP-1 receptor antagonist significantly decreased reporter cell recruitment to bone infused with UHMWPE particles and decreased osteolysis. Systemic migration of reporter cells to infused particles was decreased when the reporter cells were deficient in the CCR2 receptor. Interruption of the MCP-1 ligand-receptor axis appears to be a viable strategy to mitigate trafficking of macrophages and osteolysis due to UHMWPE particles.     

Conflicts of interest with the hand surgeon's relationship with industry

Many advances in hand surgery have been supported and enabled by the integral relationship that exists between the profession of hand surgery and industry. This relationship takes many forms, including medical education, development of new technology and methodology, research, and opportunities for patient education. As with all of these endeavors, the primary focus of both the physician and industry must be the care of the patient. When a collaborative relationship exists between physicians and industry, a conflict of interest is present and must be recognized as such and managed to avoid any detriment to patient care. Although the hand surgeon, the patient, and industry share the common interest of advancement of patient care, there does exist real and potential conflicts of interest, which are unavoidable, but not necessarily undesirable. Multiple guidelines exist to govern relationships between industry and physicians. The cooperative relationship between the physician and industry is not only helpful, but it can be critical to the advancement of and innovations in patient care. When properly managed, collaboration between the physician and industry can effectively achieve the common goal of serving the best interest of the patient.