‘Understanding Disability’: Evaluating a contact-based approach to enhancing attitudes and disability literacy of medical students

Background

Health disparities and disparities in the provision of healthcare to people with disabilities remains a topic of concern. Research demonstrates that attitudes of healthcare providers contribute to this disparity. The approach to disability education and training in medical school warrants evaluation.

California Wildfires of 2008: Coarse and Fine Particulate Matter Toxicity

Background

During the last week of June 2008, central and northern California experienced thousands of forest and brush fires, giving rise to a week of severe fire-related particulate air pollution throughout the region. California experienced PM_10–2.5 (particulate matter with mass median aerodynamic diameter > 2.5 μm to < 10 μm; coarse ) and PM_2.5 (particulate matter with mass median aerodynamic diameter < 2.5 μm; fine) concentrations greatly in excess of the air quality standards and among the highest values reported at these stations since data have been collected.

Objectives

These observations prompt a number of questions about the health impact of exposure to elevated levels of PM_10–2.5 and PM_2.5 and about the specific toxicity of PM arising from wildfires in this region.

Methods

Toxicity of PM_10–2.5 and PM_2.5 obtained during the time of peak concentrations of smoke in the air was determined with a mouse bioassay and compared with PM samples collected under normal conditions from the region during the month of June 2007.

Results

Concentrations of PM were not only higher during the wildfire episodes, but the PM was much more toxic to the lung on an equal weight basis than was PM collected from normal ambient air in the region. Toxicity was manifested as increased neutrophils and protein in lung lavage and by histologic indicators of increased cell influx and edema in the lung.

Conclusions

We conclude that the wildfire PM contains chemical components toxic to the lung, especially to alveolar macrophages, and they are more toxic to the lung than equal doses of PM collected from ambient air from the same region during a comparable season.     

Ovalbumin-Induced Airway Inflammation and Fibrosis in Mice Also Exposed to Ultrafine Particles

A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ultrafine particles (PM_2.5) on airway inflammation and remodeling. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells. Alterations in lung structure (airway remodeling and fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways and by histological evaluation of stained lung sections. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after 6 exposures over a period of 2 wk to 235 ug/m³ of PM_2.5. Mice exposed to ovalbumin for 6 wk with concurrent exposure to PM_2.5 during wk 5–6 had a significant decrease in the total number of cells recovered by lavage as compared with the group exposed to ovalbumin alone. There were no significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and PM_2.5 under the protocols studied. Airway structural changes (remodeling) were examined by three different quantitative methods. None of the groups exposed to ovalbumin and PM had a significant increase in airway collagen content evaluated biochemically (i.e., total airway collagen) as compared to the matched groups of mice exposed to ovalbumin alone. Airway collagen content evaluated histologically by sirius red staining showed significant increases in all of the animals exposed to ovalbumin, with or without PM, and no apparent difference between the ovalbumin group and mice exposed to PM with ovalbumin. The findings were consistent with an additive, or less than additive, response of mice to exposure to PM and ovalbumin. Air or PM exposure alone for 2 wk did not result in observable goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 4 wk had about 20–25% goblet cells in their conducting airways. Sequential exposure to ovalbumin and PM (or vice versa) caused significant increases in goblet cells (to about 35% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to PM_2.5, the lung inflammatory response and airway remodeling may be modified, but that this altered response is dependent upon the sequence of exposure and the duration of exposure to ovalbumin aerosol. At the concentrations of PM tested, we did not see changes in airway fibrosis or airway reactivity for animals exposed to ovalbumin and PM_2.5 as compared with animals exposed only to ovalbumin aerosol. However, goblet-cell hyperplasia was significantly increased in mice exposed concurrently to ovalbumin and PM_2.5 as compared with mice exposed to ovalbumin alone.     

An analysis of Liberia's 2007 national health policy: lessons for health systems strengthening and chronic disease care in poor, post-conflict countries

Background

Globally, chronic diseases are responsible for an enormous burden of deaths, disability, and economic loss, yet little is known about the optimal health sector response to chronic diseases in poor, post-conflict countries. Liberia's experience in strengthening health systems and health financing overall, and addressing HIV/AIDS and mental health in particular, provides a relevant case study for international stakeholders and policymakers in other poor, post-conflict countries seeking to understand and prioritize the global response to chronic diseases.

Methods

We conducted a historical review of Liberia's post-conflict policies and their impact on general economic and health indicators, as well as on health systems strengthening and chronic disease care and treatment. Key sources included primary documents from Liberia's Ministry of Health and Social Welfare, published and gray literature, and personal communications from key stakeholders engaged in Liberia's Health Sector Reform. In this case study, we examine the early reconstruction of Liberia's health care system from the end of conflict in 2003 to the present time, highlight challenges and lessons learned from this initial experience, and describe future directions for health systems strengthening and chronic disease care and treatment in Liberia.

Results

Six key lessons emerge from this analysis: (i) the 2007 National Health Policy's 'one size fits all' approach met aggregate planning targets but resulted in significant gaps and inefficiencies throughout the system; (ii) the innovative Health Sector Pool Fund proved to be an effective financing mechanism to recruit and align health actors with the 2007 National Health Policy; (iii) a substantial rural health delivery gap remains, but it could be bridged with a robust cadre of community health workers integrated into the primary health care system; (iv) effective strategies for HIV/AIDS care in other settings should be validated in Liberia and adapted for use in other chronic diseases; (v) mental health disorders are extremely prevalent in Liberia and should remain a top chronic disease priority; and (vi) better information systems and data management are needed at all levels of the health system.

Conclusions

The way forward for chronic diseases in Liberia will require an increased emphasis on quality over quantity, better data management to inform rational health sector planning, corrective mechanisms to more efficiently align health infrastructure and personnel with existing needs, and innovative methods to improve long-term retention in care and bridge the rural health delivery gap.     

Susceptibility to ovalbumin-induced airway inflammation and fibrosis in inducible nitric oxide synthetase-deficient mice: mechanisms and consequences

In a previous study, we showed that BALB/c mice demonstrate significant increases in accumulation of airway collagen after 4 weeks of exposure to ovalbumin aerosol. In the current study we examined the response to ovalbumin aerosol of a different strain of mice, C57BL/6, and compared this response to an otherwise isogenic C57BL strain (iNOS(-/-)) in which the gene for inducible nitric oxide synthetase (iNOS) had been knocked out. We hypothesized that C57BL mice, a Th-1-responsive strain, would be relatively resistant to ovalbumin exposure compared with our previous observations in the BALB/c strain, a Th-2 responder. Our results are consistent with this hypothesis, especially with respect to the accumulation of collagen in the airways of the mice exposed to ovalbumin and increased airway reactivity to challenge with methacholine, as measured by the Penh response. Since NO participates in multiple signal transduction pathways, there was no a priori reason to predict whether iNOS(-/-) mice would be more or less susceptible to allergen-induced airway inflammation than their parental wild-type strain. Responses to ovalbumin exposure of the Th-1-responsive C57BL animals were significantly less (or slower) than those we observed with the iNOS(-/-) mice. Significant increases in airway collagen content were seen only after 6 weeks of exposure of the C57BL mice, as contrasted with 4 weeks in the iNOS(-/-) animals. At each time point examined, Penh values for the iNOS(-/-) mice were significantly increased, while no increases were observed with the C57BL strain. Thus, the iNOS(-/-) mice are more susceptible to ovalbumin-induced airway inflammation and fibrosis than the C57BL strain, giving results intermediate between the previous observations in BALB/c mice and our current findings in C57BL animals with the various assays performed. We also asked whether the effects of knocking out the iNOS gene were exerted before or after the release of TGF-beta(1) by eosinophils and other effector cells in the lung. We measured the response of C57BL and iNOS(-/-) mice to direct intratracheal challenge with TGF-beta(1). There was no apparent response of C57BL mice to TGF-beta(1) at 4 or 11 days after TGF-beta(1) challenge, as evaluated by bronchoprovocation testing. On the other hand, the observed Penh values were significantly greater in iNOS(-/-) mice that had also received TGF-beta(1) 4 days previously. These results strongly support the hypothesis that the increased sensitivity of iNOS(-/-) mice to ovalbumin is at least partially dependent on pathways that come into play subsequent to the release of TGF-beta(1) by effector cells in the lungs of mice exposed to ovalbumin aerosol.     

Measuring quality of life in children with inflammatory bowel disease: The Impact-II (NL)

Inflammatory bowel disease (IBD) is a chronic debilitating disorder. Measures of quality of life are only available for adult patient populations. We developed a new disease-specific health-related quality of life instrument in Dutch for pediatric patients with IBD, called Impact-II (NL). We translated and strongly modified the original (Canadian) Impact questionnaire. It comprises 35 items in six domains. Eighty-three children (66%rpar; completed the questionnaire, 39 children were assessed twice. Disease symptoms were recorded and disease course severity assessed through chart review. Summated disease activity scores and disease course severity scores were dichotomized into two categories. Reliability coefficients were good for five out of six domains (Cronbach's ranged from 0.57 to 0.86) and measures of test–retest stability in clinically stable patients were good for all domains (intra-class correlation coefficients ranged from 0.67 to 0.91). The instrument showed good discriminant validity between symptom groups and disease course severity on all domains. Convergent validity with a validated generic instrument [TNO-AZL Children's Quality of life questionnaire (Tacqol)] showed satisfactory coefficients. In conclusion, the developed questionnaire shows good psychometric properties. Test–retest stability and responsiveness to change should be further assessed in larger patient samples. Cross-cultural translation and validation procedures into other languages are being conducted to enable international use of Impact-II.     

Mechanism of inhibition of lysyl hydroxylase activity by the organophosphates malathion and malaoxon.

Direct inhibition of lysyl hydroxylase by malathion and malaoxon was observed in an in vitro enzyme assay with recombinant lysyl hydroxylase expressed via a baculoviral system. The IC50 values for malathion and malaoxon were estimated to be approximately 60 and 45 mM, respectively. Additional kinetic studies showed this inhibition to be competitive or partially competitive with respect to the synthetic (collagen) peptide, partially uncompetitive with respect to Fe(2+), and partially noncompetitive with respect to ascorbic acid. The calculated values for the K(i) were consistent with the IC50 values. Allosteric effects were not found for any of the cofactors tested, the peptide substrate, or the inhibitors. Interactions were found to be unimolecular for lysyl hydroxylase and its substrate and cofactors as well as for the inhibitors malathion and malaoxon. A computer search of a protein structure database showed an unexpected region of partial homology between the active site sequence of acetylcholinesterase and a segment of lysyl hydroxylase, suggesting a possible molecular basis for these observations. These results suggest the possibility of a novel and hitherto unexpected class of inhibitors of lysyl hydroxylase, based on the organophosphate structure, that might be of value for testing as antifibrotic drugs.     

Supportive groups for siblings of pediatric oncology patients: impact on anxiety.

Childhood cancer can have a substantial emotional impact on the siblings of the sick child. In order to help these siblings adjust to the illness, supportive groups were started in 1994 at our medical center. The program is based on a model of psychosocial support; the aim of the group is to enhance control strategies and, thus, to reduce anxiety. It consists of five sessions and is offered to siblings aged 7-18. The study objective is to evaluate the effect of group participation on sibling anxiety. The State Trait Anxiety Inventory for Children was administered to 24 siblings before and after group participation. Results showed that siblings experience less anxiety after participating in the group. Before group participation, a majority of the siblings were more anxious compared with normal peers. The sibling's age and sex, whether the ill child is in treatment, survival perspective, and time since diagnosis were not related to anxiety reduction. The continuation of the group is supported by its positive impact on siblings. Results must nevertheless be interpreted cautiously, considering the small number of siblings participating in the study, the lack of a control group and the restriction to one outcome measure.     

Psychiatric illness in the mothers of anxious children

The authors compared maternal lifetime psychiatric illness for children with separation anxiety disorder and/or overanxious disorder (N = 58) and for children who were psychiatrically disturbed but did not manifest an anxiety or affective disorder (N = 15). The vast majority (83%) of mothers of children with separation anxiety disorder and/or overanxious disorder had a lifetime history of an anxiety disorder. Moreover, over one-half (57%) of the mothers presented with an anxiety disorder at the same time at which their children were seen for similar problems. Both of these rates significantly differed from those obtained for control subjects.