Cellular characteristics of non‐allergic eosinophilic conjunctivitis

Purpose: This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non‐allergic eosinophilic conjunctivitis (NAEC). Methods: Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin‐prick tests (the AEC group) and seven had negative skin‐prick tests (the NAEC group). Eight asymptomatic subjects with negative skin‐prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase‐positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. Results: The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Conclusions: Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course.     

Peer Reviewed: Developing a Telephone Assessment of Physical Activity (TAPA) Questionnaire for Older Adults

Introduction

We report on development and preliminary validation of a brief, telephone-based measurement tool for assessing physical activity in older adults. The Telephone Assessment of Physical Activity (TAPA) questionnaire is based on the University of Washington Health Promotion Research Center''s Rapid Assessment of Physical Activity (RAPA), a written questionnaire.

Methods

The Rapid Assessment of Physical Activity questionnaire was modified to permit interviewers to administer it as a telephone interview. We retained its scoring levels and interpretation. The pilot test of the telephone version assessed the questionnaire''s ease of administration and construct validity in a community-based sample of older adults. Spearman rho and kappa statistics were computed for comparison with the Rapid Assessment of Physical Activity questionnaire and the Community Healthy Activities Model Program for Seniors questionnaire.

Results

Thirty-four older adults completed the telephone assessment. A Spearman rho of 0.74 and a kappa statistic of 0.48 were found between TAPA and the written RAPA.

Conclusion

The pilot test demonstrated that the TAPA questionnaire is a promising instrument for use as a brief, telephone-based questionnaire for assessing physical activity in older adults.     

The South Karelia Air Pollution Study: Effects of Low-Level Exposure to Malodorous Sulfur Compounds on Symptoms

Exposure to very low levels of ambient-air malodorous sulfur compounds and their effect on eye irritation, respiratory-tract symptoms, and central nervous system symptoms in adults were assessed. A cross-sectional self-administered questionnaire (response rate = 77%) was distributed during March and April 1992 to adults (n = 336) who lived in a neighborhood that contained a pulp mill and in a nonpolluted reference community (n = 380). In the exposed community, the measured annual mean concentrations of total reduced sulfur compounds and sulfur dioxide measured in two stations were 2 to 3 μg/m³ and 1 μg/m³, respectively. In the reference community, the annual mean concentration of sulfur dioxide was 1 μg/m³. The residents of the community near the pulp mill reported an excess of cough, respiratory infections, and headache during the previous 4 wk, as well as during the preceding 12 mo. The relative risk for headache was increased significantly in the exposed community, compared with the reference area: the adjusted odds ratio (aOR) was 1.83 (95% confidence interval [95% CI] = 1.06–3.15] during the previous 4 wk and 1.70 (95% CI = 1.05–2.73) during the preceding 12 mo. The relative risk for cough was also increased during the preceding 12 mo (aOR = 1.64, 95% CI = 1.01–2.64). These results indicated that adverse health effects of malodorous sulfur compounds occur at lower concentrations than reported previously.     

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.     

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Background  To investigate tear fluid concentration of matrix metalloproteinase 8 (MMP–8) and its relation to conjunctival inflammatory cell infiltration in persistent non—allergic eosinophilic conjunctivitis (NAEC). Methods  Two groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP–8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP–8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples. Results  The mean MMP–8 concentration was significantly higher among NAEC patients (214.3 ± 327.7 μg/l) than among healthy persons (50.4 ± 62.3 μg/l, P < 0.0001). In the NAEC patients, tear fluid MMP–8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54 for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P = 0.0741). By immunocytology, MMP–8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group. Conclusions  The results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP–8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).     

Serum soluble interleukin-2 receptor level and immunophenotype are prognostic factors for patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. Although many studies have attempted to identify prognostic factors, most have focused on conventionally treated patients. The influence of anti-CD20 antibody (rituximab) should be considered now. We evaluated the prognostic significance of serum soluble interleukin-2 receptor levels and germinal center B-cell-like or non-germinal center B-cell like subgroups in 80 patients with diffuse large B-cell lymphoma, who had been treated with rituximab. Serum soluble interleukin-2 receptor levels ranged from 322 to 39900 U/mL (median 1365 U/mL). Sixteen (20%) were germinal center B-cell-like subgroups, and the remainder (80%) non-germinal center B-cell-like. Survival analysis associated lower serum soluble interleukin-2 receptor level and germinal center B-cell-like phenotype with better overall survival ( P =  0.015), whereas multivariate analysis, including International Prognostic Index factors, revealed that only higher performance status score and higher serum lactate dehydrogenase levels significantly affected survival. However, serum soluble interleukin-2 receptor levels were elevated in patients with higher International Prognostic Index scores as well as in the non-germinal center B-cell-like subgroup. Serum soluble interleukin-2 receptor levels, International Prognostic Index, and subphenotypes were strongly correlated with each other. Our study showed that soluble interleukin-2 receptor is quite useful and may serve as a substitute for the International Prognostic Index, especially for patients undergoing treatment. Moreover, the differentiation between the germinal center B-cell-like and non-germinal center B-cell-like phenotypes is also useful for predicting patients with diffuse large B-cell lymphoma, even among those treated with rituximab. ( Cancer Sci 2009; 100: 1255–1260)     

Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E₂ (PGE₂) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE₂ and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE₂ and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE₂ and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE₂ and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE₂ and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE₂ and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.     

Cochlear implant and vestibular function.

OBJECTIVES: To document incidences of vestibular dysfunction after cochlear implantation and investigate why it occurs. This work was also motivated by a desire to provide the basis for better preoperative counseling and postoperative vestibular therapy to cochlear implant patients. SETTING: Melbourne Cochlear Implant Clinic at a tertiary referral hospital. STUDY DESIGN: Prospective observational study. PATIENTS: One hundred forty-six adult implant recipients, mean age, 60 years (range, 20-90 yr). MAIN OUTCOME MEASURES: Postoperative vestibular disturbance was defined as symptoms lasting for 1 week or longer after surgery. The differences in preoperative and postoperative vestibular function were measured from subjective assessments (Dizziness Handicap Inventory and Activity Balance Confidence questionnaires) and objective assessments (bithermal caloric tests). The position of the postoperative electrode was classified as "loose", "regular", or "tight" fitting. RESULTS: Thirty-two percent of patients reported vestibular disturbance and had poorer Dizziness Handicap Inventory, Activity Balance Confidence, and caloric results in the implanted ear after surgery. Patient age, cause, and preoperative caloric result did not predict postoperative vestibular symptoms. Recipients aged 70 years or older had significantly poorer caloric results on the implanted side after surgery that was not related to the intracochlear electrode position or surgical team. CONCLUSION: One-third of recipients can expect to experience a significant vestibular disturbance after surgery, regardless of age, cause, or preoperative caloric result. "Older" ears seem more prone to permanent injury after cochlear implantation.