Barriers, strategies, and lessons learned from complementary and alternative medicine curricular initiatives.

Fifteen U.S. academic programs were the recipients of a National Center for Complementary and Alternative Medicine R25 Education Grant Program to introduce curricular changes in complementary and alternative medicine (CAM) in their institutions. The authors describe the lessons learned during the implementation of these CAM education initiatives. Principal investigators identified these lessons along with discovered barriers and strategies, both those traditionally related to medical and nursing education and those unique to CAM education. Many lessons, barriers, and strategies were common across multiple institutions. Most significant among the barriers were issues such as the resistance by faculty; the curriculum being perceived as too full; presenting CAM content in an evidence-based and even-handed way; providing useful, reliable resources; and developing teaching and assessment tools. Strategies included integration into existing curriculum; creating increased visibility of the curriculum; placing efforts into faculty development; cultivating and nurturing leadership at all levels in the organization, including among students, faculty, and administration; providing access to CAM-related databases through libraries; and fostering efforts to maintain sustainability of newly established CAM curricular elements through institutionalization and embedment into overall educational activities. These lessons, along with some detail on barriers and strategies, are reported and summarized here with the goal that they will be of practical use to other institutions embarking on new CAM education initiatives.     

Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-{kappa}B

Newcastle disease virus (NDV) has received much attention recentlybecause of its non-specific immune stimulating potential andits various anti-tumor activities. Here we describe that NDVinduces synthesis of NO and causes an activation of nuclearfactor-kB (NF-kB) In murine macrophages. These reactions werepart of an activation process which included also stimulationof adenosine deaminase and inhibition of 5'-nucleotidase. NDV-mediatedNO synthesis and NF-kB activation were blocked by an antioxidant(butylated hydroxyanisole), by an inhibitor of protein tyrosinekinase (genistein) and of protein kinase A (H-89), but not byan inhibitor of protein kinase C (staurosporin). These datasuggest that signalling requirements of NF-kB activation andNO production in NDV-treated macrophages are similar.     

Mutual inhibition of the binding of Clq and protein A to rabbit IgG immune complexes

A complex of rabbit IgG antibody with horseradish peroxidase covalently linked to Sepharose 4B was used as an insoluble immune complex for studying the binding of complement factor C1q protein A from Staphylococcus aureus, and its IgG-binding fragments AB and B, to rabbit IgG. It was shown that protein A (mol. wt approx. 42,000) and fragments AB and B (mol. wts approx. 14,000 and 7000, respectively) inhibited the binding of C1q to insoluble immune complex at 4 degrees C. However, at 37 degrees C fragment B did not inhibit this binding. On the other hand, C1q, when bound to an insoluble immune complex, almost completely blocked the binding of protein A and fragment B at both temps. The higher affinity of C1q for its CH2-binding site than of fragment B for its CH2-binding site may explain the displacement of the latter from the CH2 domain. The mutual inhibition of the binding of C1q and protein A (and its smaller fragments) indicates that the binding sites for C1q and protein A are closely located in the CH2 domain.     

Effect of immunotherapy on appearance of antibodies to ragweed in external secretions

Studies on 50 nasal washings, 16 parotid salivas from ragweed-allergic patients, and 10 secretions from normal subjects showed considerable variation in protein and immunoglobulin concentrations. Only 2 immunoglobulins, A and G, were found in nasal washings. Of 26 parotid salivas studied (allergic and controls), IgA was found in 26, IgG in 4, and IgM in 3 specimens. Anti-ragweed antibodies in the serum and exocrine secretions of allergic patients were examined by means of Prausnitz-Küstner (PK) test, radioimmunoelectrophoresis, radioimmunodiffusion, and tanned cell hemagglutination (TH) tests. The incidence of IgE, IgA, and IgG antibodies to ragweed in the sera and nasal washings in a group of 22 patients with previous immunotherapy was compared to that of 28 patients without immunotherapy. The immunotherapy seemed to affect the incidence of serum IgE and IgG antibodies but has no influence on the incidence of anti-ragweed antibodies in the nasal washings. PK activity of nasal washings could be removed by absorption with anti-IgE but not anti-IgA or anti-IgG immunosorbents. Anti-ragweed antibodies could be detected in parotid salivas only by the TH test.     

Mechanical and Cellular Changes During Compaction of a Collagen-Sponge-Based Corneal Stromal Equivalent

The need for corneas suitable for transplantation, combined with the decreasing supply, has fueled interest in the development of a corneal replacement. In this study, a collagen-sponge-based stromal equivalent, consisting of human corneal fibroblasts cultured on a type I collagen sponge, was maintained in culture for up to 21 days and characterized with respect to mechanical properties and cellular behavior. The Young's modulus of the stromal equivalent varied from 95 to 370 Pa, and its permeability varied from 5.3 x 10(-8) - 4.2 x 10(-7) m4 N(-1) s(-1). The greatest changes occurred during the first few days in culture, but the mechanical properties continued to change during the entire 21 days. Cell traction stress, determined from sponge compaction and DNA count, decreased during the compaction process with the maximum traction value the initial value of 6.6 +/- 2.9 x 10(-3) Pacm3 cell(-1). Microarray data showed that the expression level of fibronectin, decorin sulfate, collagenase, and gelatinase A was upregulated at day 14 in the sponge. This suggested that the repair fibroblast phenotype was being expressed by the fibroblasts. Additional analysis suggested that a subpopulation of cells expressed the myofibroblast phenotype.     

On the classification of the acrocephalosyndactyly syndromes

This report describes a family in which two different types of acrocephalosyndactyly (ACS) were clinically identified. The proband presented with the classic stigmata of Pfeiffer syndrome, while her cousin was considered to be a typical case of Apert syndrome. Seven other family members also have unusually shaped heads and the facial appearance reminiscent of Crouzon disease.
Observations made in this family and from previous reports in the literature, we feel there is substantial reason to re-evaluate the ACS classification and to consider that the Apert and Pfeiffer types of ACS may be one and the same.     

Identifying amino acid residues that influence plasma clearance of murine IgG1 fragments by site-directed mutagenesis

Site-directed mutagenesis has been used to change amino acid residues of a recombinant Fc-hinge fragment derived from the murine immunoglobulin (Ig)G1 molecule, and the effects of these mutations on the pharmacokinetics of the Fc-hinge fragment have been determined. Specifically, Ile-253, His-310 and Gln-311 of the CH2 domain and His-433 and Asn-434 of the CH3 domain have been changed. In the three dimensional structure of an antibody, these amino acids are in close proximity to each other at the CH2-CH3 domain interface. The mutated Fc-hinge fragments have been purified from recombinant Escherichia coli cells and their pharmacokinetic parameters determined in mice and compared with those of the wild-type Fc-hinge fragment. The results show that the site of the IgG1 molecule that controls the catabolic rate (the ‘catabolic site’) is located at the CH2-CH3 domain interface and overlaps with the Staphylococcal protein A binding site.     

Detection of human perforin by ELISpot and ELISA: ex vivo identification of virus-specific cells

The perforin (PFN) protein is essential for the elimination of target cells by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. The study of cells releasing PFN has been hampered by a lack of sensitive methods. We therefore produced PFN-reactive monoclonal antibodies (mAb) and developed capture enzyme-linked immunosorbent (ELISA) and enzyme-linked immunospot (ELISpot) assays. Three mAbs were generated and shown to react with unique determinants of PFN. All mAbs recognized intracellular PFN in human peripheral blood mononuclear cell (PBMC) as assessed by flow cytometry and immunohistochemistry. Functional PFN capture ELISA and ELISpot assays were developed utilizing two of the mAbs for capture and the third mAb for detection. When examining PFN release by the YT lymphoma cell line, the ELISpot displayed a greater detection sensitivity than the ELISA. Assessment of PFN release by a CTL clone using ELISpot gave results consistent with a parallel (51)Cr-release cytotoxicity assay. Moreover, PFN release by PBMC could be quantified by ELISpot and ELISA after ex vivo stimulation with defined CTL epitopes from common viruses. These novel immunoassays will be valuable for further investigations of the mechanisms underlying granule-mediated apoptosis. In addition, the capture immunoassays could provide tools for studying CTL responses in infectious and tumor diseases as well as for vaccine development.     

Integration of the biopsychosocial model: perspectives of medical students and residents.

PURPOSE: To examine residents' and medical students' attitudes toward the incorporation of psychosocial factors in diagnosis and treatment and to identify barriers to the integration of evidence-based, mind-body methods. METHOD: A random sample of third- and fourth-year medical students and residents was drawn from the Masterfiles of the American Medical Association. A total of 661 medical students and 550 residents completed a survey, assessing attitudes toward the role of psychosocial factors and the clinical application of behavioral/mind-body methods. RESULTS: The response rate was 40%. Whereas a majority of students and residents seem to recognize the need to address psychosocial factors, 30%-40% believe that addressing such factors leads to minimal or no improvements in outcomes. The majority of students and residents reports that their training in these areas was ineffective, yet relatively few indicate interest in receiving further training.Females are more likely to believe in the need to address psychosocial factors. Additional factors associated with greater openness to addressing psychosocial factors include (1) the perception that training in these areas was helpful, and (2) personal use of behavioral/mind-body methods to care for one's own health. CONCLUSIONS: There is a need for more comprehensive training during medical school and residency regarding both the role of psychosocial factors in health and the application of evidence-based, behavioral/mind-body methods. The current health care structure-particularly insufficient time and inadequate reimbursement for addressing psychosocial factors-may be undermining efforts to improve patient care through inconsistent or nonexistent application of the biopsychosocial model.     

Heritability and clinical features of multigenerational families with obsessive-compulsive disorder and hoarding.

To date, only one complete genome screen for obsessive-compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood-onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive-compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding.