Induction of aggrecanase 1 (ADAM-TS4) by interleukin-1 occurs through activation of constitutively produced protein

OBJECTIVE: To study the production of aggrecanase 1 (ADAM-TS4) in monolayer chondrocytes, capsular fibroblasts, and cartilage. METHODS: Bovine nasal and articular cartilage, monolayer chondrocytes, and capsular fibroblasts were incubated in the absence and presence of interleukin-1 (IL-1). ADAM-TS4 production was evaluated by immunofluorescence or by Western blot analysis. Aggrecanase activity was measured in cells grown on an immobilized peptide substrate, and peptide cleavage was monitored by enzyme-linked immunosorbent assay. RESULTS: There was constitutive production of ADAM-TS4 in both cells and tissue. The protein was associated with the extracellular matrix based on the observation that the staining could be reduced following treatment of chondrocytes with heparin or exposure to chondroitinase ABC. Interestingly, there was no detectable change in the abundance of ADAM-TS4 in response to IL-1. Western blot analysis of cell lysates from IL-1-stimulated chondrocytes showed no evidence of increased ADAM-TS4 production, but resulted in activation of ADAM-TS4. The activation was associated with an increased generation in the aggrecanase neoepitope NITEGE in nasal cartilage in response to IL-1. These data suggest that induction of aggrecanase activity both in cells and in cartilage by IL-1 may involve the stimulation of an activator of ADAM-TS4. Consistent with this observation, culture of chondrocytes on a solid support containing a peptide substrate resulted in the generation of aggrecanase-mediated cleavage that could be blocked by selective inhibitors of ADAM-TS4. CONCLUSION: These data support the hypothesis that ADAM-TS4 is constitutively produced in these cells and tissue, and that stimulation by IL-1 results in aggrecanase activation. Thus, the activator could be a potential target by which to control aggrecanase-mediated degradation in arthritic diseases.     

CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer with a cure rate of approximately 80%. Relapse occurs despite treatment stratification based on clinical criteria. Relapse risk in ALL may be related to simple nucleotide polymorphisms (SNPs) of enzymes that metabolize chemotherapeutic agents. We evaluated whether SNPs in the cytochrome P450 3A family (CYP3A4*1B, CYP3A5*3 and CYP3A5*6) were associated with relapse risk on a national Children's Cancer Group (CCG) paediatric ALL trial (CCG-1891). CCG-1891 enrolled 1204 patients, and obtained both relapse and toxicity data prospectively. One hundred and twenty-four relapsed patients and 409 non-relapsed patients were assayed for each SNP. CYP3A variants were not associated with an increased risk of relapse. However, patients with the CYP3A4*1B and CYP3A5*3 genotypes had a decreased risk of peripheral neuropathy that was statistically significant on univariate analysis. After correction for multiple comparisons, the association between CYP3A*1B and CYP3A5*3 genotypes approached, but did not reach, statistical significance. CYP3 genotypes may not significantly modify the risk of relapse in childhood ALL, but may modify the risk of toxicity.     

Attitudes toward seeking treatment among alcohol-using college students

Past research indicates that many college students engage in heavy drinking and that these drinking patterns oftentimes lead to alcohol-related problems. The current study contributes to the literature on college drinking by investigating treatment-seeking attitudes among students in relation to their alcohol education background, alcohol environment, alcohol consumption, and perceived and actual drinking problems. A total of 878 students from five New York State colleges were randomly selected through the use of complete student telephone directories provided by students' respective college administrations for a telephone interview. The results revealed that alcohol education increases students' positive attitudes toward treatment, which may help them to reduce their heavy drinking and alcohol problems.     

Correlates of IL-10 and IL-12 concentrations in cervical secretions

Interindividual variations in host immune responses to HPV infection are thought to be important determinants of viral persistence and progression to cervical intraepithelial neoplasia and cancer. However, few studies have measured local immune markers at the site of infection (e.g., the cervical mucosa). We sought to determine biologic correlates of IL-10 and IL-12 concentrations in cervical secretions. Cervical secretions were passively collected using a WeckCel sponge from 247 women participating in a natural history study of human papillomavirus infection as part of an immunologic ancillary study. IL-10 and IL-12 concentrations were determined using standard ELISA assays.In general, IL-10 and IL-12 levels were significantly intercorrelated (Pearson's correlation coefficient = 0.6) but had somewhat different determinants. Significant increases (P < 0.05) in IL-10 concentrations were observed for nonovulatory phases of the menstrual cycle, postmenopausal status, recent use of oral contraceptives (OC), low secretion volume, macrolevels of heme contamination, and high vaginal pH. Increasing IL-10 levels were also observed among smokers, women with increasing numbers of lifetime sex partners, and women who report having less frequent sex (less than once per week), however, these results were not statistically significant. Significantly higher IL-12 concentrations were observed among recent OC users, women with low secretion volume, and women with a high vaginal pH. There was a non-statistically significant observation of increasing IL-12 levels among nonsmokers, women with increasing numbers of lifetime and recent pregnancies, and increasing levels of heme contamination. We failed to observe a significant association between HPV and IL-10 or IL-12 levels in this cross-sectional sample. Future analyses of cervical cytokine levels and HPV infection should control for the inherent variation of local cytokine levels due to hormonal influences, hemoglobin contamination, pH, and cervical secretion volume differences.     

Approaches to quality improvement in nursing homes: Lessons learned from the six-state pilot of CMS's Nursing Home Quality Initiative

Background  

In November 2002, the Centers for Medicare & Medicaid Services (CMS) launched a Nursing Home Quality Initiative that included publicly reporting a set of Quality Measures for all nursing homes in the country, and providing quality improvement assistance to nursing homes nationwide. A pilot of this initiative occurred in six states for six months prior to the launch.     

Development of an asthma disease management program in a children’s hospital

The incidence, morbidity, and mortality of asthma have been increasing at an alarming rate, making asthma the most common chronic illness of childhood. An asthma disease management program was developed to improve the care and management of patients with asthma—a comprehensive health care delivery model that was designed to improve the management of patients with asthma was designed and implemented. The goal of the program was to provide high-quality interventions for those children diagnosed with asthma. The asthma disease management program at Children’s Mercy Hospital improved the care received, decreased costs, and improved the quality of life for those children with asthma.     

Analysis of the nursing workforce crisis: a call to action

In our integrative review of reports on the health care workforce shortage, we examined 15 reports that focused primarily on nursing and were conducted by various stakeholders. We studied these reports objectively, identifying problems and solutions as described by the authors, which we then categorized by theme. We found problems at both the national and institutional levels and noted that the reports contained similar problem and solution "themes." Yet we also found gaps between these-some problems had no solutions and some solutions didn't address any of the suggested problems. Gaps occurred among problems and solutions listed in the following theme categories: demand, health care economics, workforce planning, research and data support, and technology.Despite the urgent need, we still lack a national strategy designed to avert the nursing shortage. This review may provide a foundation for such a plan.We present the results of our analysis and our recommendations to the federal government and national organizations, to institutions, and to nurses. These recommendations don't provide a comprehensive strategy for averting the nursing shortage, but they do offer a basis upon which one may be created.     

"Razoo Health": a community-based nursing education initiative

When statistics depicted a health crisis for people of all ages living in Louisiana, and New Orleans in particular, school of nursing faculty designed and instituted a neighborhood-based initiative to "Razoo Health." This initiative facilitated a paradigm shift from exclusively illness management to include health promotion and disease prevention. "Razoo," a local colloquialism used to claim an opponent's marble during game play, means to snatch or claim. Appropriately, Razoo Health refers to the intent of Louisiana citizens to reclaim and take back the health of the people in the cities' neighborhoods. Working with four inner-city parochial schools and churches as hubs, nursing faculty and students mobilize neighborhood assets, talents, and capacities to form partnerships for healthy change. The Centers for Disease Control and Prevention Coordinated School Health Model is employed within each neighborhood school to provide health care access, decrease absenteeism, raise test scores, and deliver worksite health programming to faculty and staff and to neighbors and parishioners. Nursing students work with citizens and students of other health care professions to learn community assessment skills and deliver primary, secondary, and tertiary services to individuals, families, and the community. Citizens wear crowns of empowered sovereignty as they take back, or razoo, what is rightfully theirs--health.     

ICD-9-CM coding from a manager's perspective

This article discusses how a clinical manager can work with staff to select the best diagnoses and ICD-9-CM code for each patient. The selection of diagnoses must be based on all available information and be directly related to the home care services provided. Case studies are presented to show application.