Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Bronchodilatory and anti-inflammatory properties of inhaled selective phosphodiesterase inhibitors in a guinea pig model of allergic asthma.

In a guinea pig model of allergic asthma, we investigated the effects of the selective phosphodiesterase inhibitors rolipram (phosphodiesterase 4-selective), Org 9935 (phosphodiesterase 3-selective) and Org 20241 (dual phosphodiesterase 4/phosphodiesterase 3-selective), administered by aerosol inhalation in approximately equipotent bronchodilatory doses, on allergen-induced early and late asthmatic reactions, airway hyperreactivity and airway inflammation. Using ovalbumin-sensitized non-challenged animals, different nebulizer concentrations of each inhibitor were tested for their protective effects against histamine-induced bronchoconstriction. Inhalation of 2.5 mM rolipram, 100 mM 4,5-dihydro-6-(5,6-dimethoxybenzo[b]thien-2-yl-5-methyl-3(2H)pyridazinone (Org 9935) and 10 and 100 mM N-hydroxy-4-(3,4-dimethoxyphenyl)-thiazole-2-carboximidamide HCl (Org 20241) provided a similar, 1.8-fold (P<0.01), 2.0-fold (P<0.05), and 1.8- and 1.9-fold (P<0.05) protection, respectively. The duration of these bronchoprotective effects were different, the rate of decline being faster with rolipram and the lower Org 20241 concentration than with Org 9935 and the higher concentration of Org 20241. All compounds strongly protected against the immediate allergen-induced bronchoconstriction and significantly (P<0.05) diminished the overall early asthmatic reaction from 0 to 6 h following allergen-provocation. The severity of the late asthmatic reaction was also significantly inhibited by rolipram (P<0.05) and Org 9935 (P<0.05). Allergen-induced airway hyperreactivity to inhaled histamine after the early reaction, at 6 h after ovalbumin challenge, was strongly reduced by rolipram (P<0.05) and completely prevented by the two other phosphodiesterase inhibitors; in addition, airway hyperreactivity after the late asthmatic reaction, at 24 h, was abolished in all treatment groups. Bronchoalveolar lavage performed at 24 h after allergen challenge revealed no inhibition of eosinophil infiltration in the rolipram-treated animals, whereas inhalation of Org 9935 and the higher-but not the lower-concentration of Org 20241 strongly reduced the influx of these cells. Eosinophil peroxidase activity in the lavage fluid tended to be diminished in all treatment groups but significance was not reached with the exception of the lower concentration of Org 20241. Infiltration of lymphocytes and macrophages was significantly inhibited by Org 9935 only (P<0.05 and P<0.01, respectively), whereas neutrophil influx was not significantly affected. The results indicate that inhalation of phosphodiesterase 3-, phosphodiesterase 4- and dual phosphodiesterase 3/phosphodiesterase 4-selective inhibitors afford protection against acute histamine- and allergen-induced bronchoconstriction and prevent the development of airway hyperreactivity both after the early and late asthmatic reaction predominantly through inhibition of phosphodiesterase 4; in contrast, for significant reduction of eosinophil infiltration, both phosphodiesterase 3 and phosphodiesterase 4 inhibition seems to be required.

Evaluation of 25-hydroxy vitamin D assay on the immunodiagnostic systems iSYS analyser.

BACKGROUND: We evaluated the recently released chemiluminescence assay for 25-hydroxy vitamin D (25-OHD) on the Immunodiagnostic Systems iSYS (IDS-iSYS) automated analyser. METHODS: The IDS-iSYS comparison was performed using patient samples previously measured for 25-OHD by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (n = 119) and an IDS enzyme immunoassy (IDS-EIA) method (n = 64). Limit of detection and limit of quantification were determined from a precision profile. Imprecision was assessed using quality control material and pooled serum. External QAP material (Vitamin D External Quality Assessment Scheme, UK) was analysed to establish inaccuracy. Linearity was assessed by two dilution studies. Cross-reactivity was determined by three serial dilution studies of patient samples with known 25-OHD(2) concentrations. RESULTS: The IDS-iSYS correlated well with both established methods (iSYS = 1.03LC-MS/MS - 6.53, R(2) = 0.82 and iSYS = 1.07IDS-EIA - 1.61, R(2) = 0.86). Imprecision of the iSYS assay for IDS control material was 13.4% at 32 nmol/L, 10% at 78 nmol/L, 9.4% at 161 nmol/L, and for the pooled material 9.3% at 72 nmol/L and 5.6% at 158 nmol/L. The evaluation found the assay to be highly accurate (IDS-iSYS = 0.93ALTM + 3.79, R(2) = 0.94) and linear (obs(1) = 0.93exp(1) - 5.05, R(2) = 0.99 (P = 0.256); and obs(2) = 0.97exp(2) + 6.07, R(2) = 0.97 (P = 0.654); ALTM, all-laboratory trimmed mean). Cross-reactivity studies demonstrated no significant difference to the calculated total 25-OHD as measured by LC-MS/MS. CONCLUSIONS: Even though the imprecision of the iSYS was found to be greater than that of the LC-MS/MS and EIA methods, the performance characteristics of the IDS-iSYS 25-OHD assay are suitable for routine diagnostic purposes on a high throughput automated analyser.