Steven J. Ackerman

A review of therapist characteristics and techniques positively impacting the therapeutic alliance

The present review is a comprehensive examination of the therapists personal attributes and in-session activities that positively influence the therapeutic alliance from a broad range of psychotherapy perspectives. Therapists personal attributes such as being flexible, honest, respectful, trustworthy, confident, warm, interested, and open were found to contribute positively to the alliance. Therapist techniques such as exploration, reflection, noting past therapy success, accurate interpretation, facilitating the expression of affect, and attending to the patients experience were also found to contribute positively to the alliance. This review reveals how these therapist personal qualities and techniques have a positive influence on the identification or repair of ruptures in the alliance.

Dermal deposition of eosinophil-granule major basic protein in atopic dermatitis: comparison with onchocerciasis

Although blood eosinophilia is commonly present in atopic dermatitis, accumulation of tissue eosinophils is not prominent. To determine whether eosinophil degranulation occurs in lesions of atopic dermatitis, we analyzed tissues by immunofluorescence for the presence of the eosinophil-granule major basic protein. Twenty biopsy specimens from 18 patients with atopic dermatitis were studied, and all showed major basic protein staining outside eosinophils. In 18 specimens, the staining was fibrillar, was located in the upper half of the dermis, and was similar to the distribution of elastic fibers. Twelve specimens with fibrillar staining also showed major basic protein staining in the form of extracellular granules. One specimen from unaffected skin showed minimal faint, fine, fluorescing fibrils, but there was marked deposition of the protein in affected skin. The fibrillar pattern of major basic protein staining in atopic dermatitis was very similar to that seen in lichenified lesions of untreated onchocerciasis. These results suggest that eosinophils commonly release granule proteins in the dermis and that assessment of eosinophil involvement in disease cannot be based simply on numbers of eosinophils in tissue.

Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease

Eosinophilic endomyocardial disease is a complication of the hypereosinophilic syndrome and of several other disorders associated with high blood eosinophil counts. Eosinophil granule proteins may be involved in the development of these lesions. This multi-centre study investigated whether these proteins could be demonstrated within the cardiac tissues of eighteen patients with eosinophilic endomyocardial disease. Serial sections of tissue taken at necropsy or at cardiac biopsy were stained for eosinophil major basic protein by indirect immunofluorescence and for eosinophil cationic protein, eosinophil protein-X, and activated eosinophils by means of alkaline-phosphatase-linked monoclonal antibodies. Activated eosinophils and secreted eosinophil granule proteins were most evident within the necrotic and later stage thrombotic lesions and were found mainly within the areas of acute tissue damage in the endocardium and in the walls of small blood vessels. These findings suggest that eosinophil granule proteins are involved in cardiac injury, producing muscle damage and vascular injury which lead to the development of endomyocardial fibrosis.

Interaction of therapeutic process and alliance during psychological assessment.

Utilizing a collaborative therapeutic assessment (TA) model proposed by Finn and Tonsager (1997), we examined the interaction between therapeutic alliance and in-session process during the assessment phase of treatment. This study compares the utility of the TA model (n = 38) versus a traditional information gathering model (n = 90) of assessment. The results of this study indicate that the use of a TA model may decrease the number of patients who terminate treatment against medical advice. The Session Evaluation Questionnaire (Stiles & Snow, 1984), Combined Alliance Short Form (Hatcher & Barends, 1996), and Penn Helping Alliance Questionnaire-Revised (Barber & Crits-Christoph, 1996) can reliably measure the patients experience of the assessment. The psychological assessment process may impact the patients experience of assessment feedback and aid in the development of a therapeutic alliance. The therapeutic alliance developed during the assessment was found to be related to alliance early in psychotherapy. We discuss the theoretical, clinical, and research implications of these findings.

The Development of Therapeutic Alliance During Psychological Assessment: Patient and Therapist Perspectives Across Treatment

We examined the impact of patient- and therapist-rated alliance developed during psychological assessment on the subsequent alliance measured early and late in formal psychotherapy. We hypothesized that a working alliance developed during psychological assessment conducted from a collaborative therapeutic model of assessment (TMA; Finn & Tonsager, 1992, 1997; Fischer, 1994) between the patient and therapist would carry into formal psychotherapy. We also hypothesized that alliance for those patients receiving a TMA would be significantly greater than patients receiving psychological testing as usual. To test this hypothesis, we administered the Combined Alliance Short Form-Patient Version (Hatcher & Barends, 1996) and the Combined Alliance Short Form-Therapist Version (Hatcher, 1999) to a sample of outpatients and their therapists at the end of the assessment feedback session, early, and late in psychotherapy. The hypotheses were supported as alliance scales rated at the assessment feedback session demonstrated positive and significant relationships with alliance throughout formal psychotherapy and in relation to a control group. The clinical utility and research implications of these findings are discussed.

The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis

Objective Eosinophil predominant inflammation characterises histological features of eosinophilic oesophagitis (EoE). Endoscopy with biopsy is currently the only method to assess oesophageal mucosal inflammation in EoE. We hypothesised that measurements of luminal eosinophil-derived proteins would correlate with oesophageal mucosal inflammation in children with EoE. Design The Enterotest diagnostic device was used to develop an oesophageal string test (EST) as a minimally invasive clinical device. EST samples and oesophageal mucosal biopsies were obtained from children undergoing upper endoscopy for clinically defined indications. Eosinophil-derived proteins including eosinophil secondary granule proteins (major basic protein-1, eosinophil-derived neurotoxin, eosinophil cationic protein, eosinophil peroxidase) and Charcot–Leyden crystal protein/galectin-10 were measured by ELISA in luminal effluents eluted from ESTs and extracts of mucosal biopsies. Results ESTs were performed in 41 children with active EoE (n=14), EoE in remission (n=8), gastro-oesophageal reflux disease (n=4) and controls with normal oesophagus (n=15). EST measurement of eosinophil-derived protein biomarkers significantly distinguished between children with active EoE, treated EoE in remission, gastro-oesophageal reflux disease and normal oesophagus. Levels of luminal eosinophil-derived proteins in EST samples significantly correlated with peak and mean oesophageal eosinophils/high power field (HPF), eosinophil peroxidase indices and levels of the same eosinophil-derived proteins in extracts of oesophageal biopsies. Conclusions The presence of eosinophil-derived proteins in luminal secretions is reflective of mucosal inflammation in children with EoE. The EST is a novel, minimally invasive device for measuring oesophageal eosinophilic inflammation in children with EoE.

Eosinophilic Esophagitis: Epithelial Mesenchymal Transition Contributes to Esophageal Remodeling and Reverses with Treatment

BACKGROUND Mechanisms underlying esophageal remodeling with subepithelial fibrosis in subjects with eosinophilic esophagitis (EoE) have not been delineated. OBJECTIVES We sought to explore a role for epithelial mesenchymal transition (EMT) in subjects with EoE and determine whether EMT resolves with treatment. METHODS Esophageal biopsy specimens from 60 children were immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT biomarkers, and EMT was quantified. Subjects studied had EoE (n = 17), indeterminate EoE (n = 15), gastroesophageal reflux disease (n = 7), or normal esophagus (n = 21). EMT was analyzed for relationships to diagnosis, eosinophil counts, and indices of subepithelial fibrosis, eosinophil peroxidase, and TGF-β immunostaining. EMT was assessed in pretreatment and posttreatment biopsy specimens from 18 subjects with EoE treated with an elemental diet, 6-food elimination diet, or topical corticosteroids (n = 6 per group). RESULTS TGF-β1 treatment of esophageal epithelial cells in vitro for 24 hours induced upregulation of mesenchymal genes characteristic of EMT, including N-cadherin (3.3-fold), vimentin (2.1-fold), and fibronectin (7.5-fold). EMT in esophageal biopsy specimens was associated with EoE (or indeterminate EoE) but not gastroesophageal reflux disease or normal esophagus and was correlated to eosinophil counts (r = 0.691), eosinophil peroxidase (r = 0.738), and TGF-β (r = 0.520) immunostaining and fibrosis (r = 0.644) indices. EMT resolved with EoE treatments that induced clinicopathologic remission with reduced eosinophil counts. EMT decreased significantly after treatment by 74.1% overall in the 18 treated subjects with EoE; pretreatment versus posttreatment EMT scores were 3.17 ± 0.82 versus 0.82 ± 0.39 (P < .001), with similar decreases within treatment groups. Pretreatment/posttreatment EMT was strongly correlated with eosinophil counts for combined (r = 0.804, P < .001) and individual treatment groups. CONCLUSIONS EMT likely contributes to subepithelial fibrosis in subjects with EoE and resolves with treatments that decrease esophageal inflammation, and its resolution correlates with decreased numbers of esophageal eosinophils.

Relationships Between Eosinophilic Inflammation, Tissue Remodeling and Fibrosis in Eosinophilic Esophagitis

The clinical and pathologic features of eosinophilic esophagitis (EE) include extensive tissue remodeling. Increasing evidence supports a key role for the eosinophil in multiple aspects of the esophageal remodeling and fibrosis seen in this allergic disease. This article reviews the clinical implications of esophageal remodeling and fibrosis in EE and discusses the possible pathogenic mechanisms inducing and regulating these responses. The focus is specifically on eosinophil and cytokine interactions with the esophageal epithelium, vascular endothelium, resident fibroblasts, and smooth muscle. Current and potential therapeutic interventions are discussed that may impact the development or resolution of chronic esophageal remodeling and fibrosis in EE.

Eosinophil granule proteins: form and function.

Experimental and clinical data strongly support a role for the eosinophil in the pathogenesis of asthma, allergic and parasitic diseases, and hypereosinophilic syndromes, in addition to more recently identified immunomodulatory roles in shaping innate host defense, adaptive immunity, tissue repair/remodeling, and maintenance of normal tissue homeostasis. A seminal finding was the dependence of allergic airway inflammation on eosinophil-induced recruitment of Th2-polarized effector T-cells to the lung, providing a missing link between these innate immune effectors (eosinophils) and adaptive T-cell responses. Eosinophils come equipped with preformed enzymatic and nonenzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules. These proteins contribute to the functions of the eosinophil in airway inflammation, tissue damage, and remodeling in the asthmatic diathesis. Studies using eosinophil-deficient mouse models, including eosinophil-derived granule protein double knock-out mice (major basic protein-1/eosinophil peroxidase dual gene deletion) show that eosinophils are required for all major hallmarks of asthma pathophysiology: airway epithelial damage and hyperreactivity, and airway remodeling including smooth muscle hyperplasia and subepithelial fibrosis. Here we review key molecular aspects of these eosinophil-derived granule proteins in terms of structure-function relationships to advance understanding of their roles in eosinophil cell biology, molecular biology, and immunobiology in health and disease.

Eosinophil Granule Major Basic Protein and Charcot-Leyden Crystal Protein in Human Tears

We measured the levels of major basic protein and Charcot-Leyden crystal protein in tears from patients with ventral keratoconjunctivitis or miscellaneous inflammatory or noninflammatory ocular conditions, and from normal subjects. Patients with vernal keratoconjunctivitis had significantly increased levels of both proteins in their tears compared with the other subjects tested; levels of major basic protein seemed to correlate with the severity of the disease. The levels of Charcot-Leyden crystal protein paralleled those of major basic proteins.