Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma.

BACKGROUND--Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS--Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS--Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS--Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy.     

Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy

BACKGROUND: Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)-dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance. OBJECTIVE: To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical 'response' as defined by oral CS reduction. METHODS: Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as 'responders' or 'non-responders' to MTX (reduction of initial oral prednisolone requirement by >or=50% or <50%, respectively). Patients were followed-up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks. RESULTS: MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX 'responders' as compared with 'non-responders', and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation. CONCLUSION: MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.     

Prospective validation of a single sample technique to determine technetium-99m-MAG3 clearance.

Technetium-99m-MAG3 clearance is proportional to OIH clearance and can be used directly as a measure of renal function. Multiple plasma sample, two-compartment clearance data from three studies were recently pooled to develop a single-sample regression equation for determining the clearance of 99mTc-MAG3. To test this published equation, a prospective study was conducted in 34 patients with a wide range of renal function. Multiple plasma samples were obtained from 9 to 60 min following the bolus injection of 99mTc-MAG3 and the clearances were calculated based on a single injection, two-compartment model. Clearances were also calculated using a single 43-min plasma sample and the published regression equation. There was an excellent correlation (r = 0.976) between the two clearances; the slope of the regression line was 1.01 with an intercept of -26.6; the standard error of the estimate was 24 ml/min. In conclusion, the current regression equation provides a good estimate of 99mTc-MAG3 clearance.     

Agitation, cognition and attention during post-traumatic amnesia

During the early phases of recovery from traumatic head injury, the level of functional cognition and the presence of agitation in patients appear to co-vary. However, it has been observed that there appears to be some temporal dissasociation in the recovery of cognition and agitation. The purpose of this study was to investigate the degree to which attention accounts for the co-variation previously observed. Over a 1-year period, 130 patient-weeks of independent monitoring of cognition, agitation and attention were obtained from 20 head-injured patients in the acute phase of recovery. Weekly scores for measures of cognition, agitation and attention were each found to share approximately 50% of the variance when paired with one of the other two. When attention was extracted, only 7% of the variation in cognition was accounted for by agitation, and 40% of the variance could not be accounted for by either agitation or attention. These results support previous findings that cognition and agitation co-vary with most of the co-variance due to the effect of attention on each. Concomitantly, these results allow that significant portions of the variance in cognition and agitation may be temporally dissociated during the acute phases of recovery from traumatic head injury.     

雷公藤多甙与棉酚合用对雄大鼠生育力的影响

本研究探讨雷公藤多甙(GTW)与棉酚合用对雄大鼠生育力的影响。SD雄大鼠用棉酚及GTW各6 mg/kg/d,灌胃给药,每周6日,共11周。10只用药动物全部不育,附睾精子密度和活率也明显下降,而体重增长如常,性行为存在。睾丸光镜下结构绝大多数无明显异常,血清睾酮水平正常,副性腺重量无明显变化。停药6周后生育力恢复。在相同剂量下,单用GTW或棉酚均无抗生育效果。表明两药合用有相加作用,为减少棉酚和GTW副作用提供一条可能途径。     

Construct Validity of a Clinical-performance-evaluation Tool in Community Health Nursing

An evaluative research study was conducted to examine the construct validity and applicability of a selected clinical-performance-evaluation tool. The tool was designed for baccalaureate students in a community health nursing course. Eighteen senior students functioning in two urban clinical agencies participated in the study. Data were collected at two evaluation points over one semester. Results indicated strong support for construct validity of the tool. This finding suggests a high level of correlation between theoretical concepts and clinical practice. Recommendations for use of the clinical performance evaluation tool are discussed.     

Schizophrenic patients' attitudes to therapists using behavioral and holistic-humanistic techniques

In a preliminary study of patients' perceptions of therapists' styles, 18 subjects with diagnoses of schizophrenia were randomly assigned either to social skills training or holistic health therapy. Four therapists conducted each treatment session in pairs, rotating between treatment conditions daily. At the end of 10 weeks of treatment, patients were able to discriminate among therapists on three interactional styles-"understanding," "independence-encouraging," and "and "critical-hostile"-and were able to differentiate between behavioral and holistic health treatments on "authoritarian" attitudes.     

Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis

BACKGROUND: Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis. OBJECTIVE: To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls. METHODS: Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis. RESULTS: The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls. CONCLUSION: Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications.     

Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid

BACKGROUND: The clinical efficacy and safety of a six-grass pollen allergoid has been studied. The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this reappraisal. METHODS: A 2-year double-blind multicentre placebo-controlled phase 3 clinical trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis with or without asthma (GINA I or II). Therapy comprised two consecutive preseasonal short-courses of subcutaneous injections using a grass pollen allergoid adsorbed to aluminium hydroxide. RESULTS: A combined symptom and medication score (SMS) was used as the primary end-point for clinical efficacy. SMS from the first year showed a significant difference of 26.6% between the two study groups (P=0.026) and this was improved after the second year when there was a 48.4% difference in SMS between active and placebo treatment in favour of the allergoid (P = 0.018). Highly significant increases in grass pollen allergen-specific IgG1 and IgG4 antibody concentrations were measured in association with active treatment. Allergen tolerance was increased as judged by a conjunctival provocation test and significant improvements in quality of life were documented using a standardized questionnaire. The allergoid was well tolerated. CONCLUSIONS: The grass pollen allergoid was shown to be safe and clinically efficacious in the management of hay fever with or without asthma (GINA I or II).