A comparison of 2 extrafine hydrofluoroalkane-134a-beclomethasone formulations on methacholine hyperresponsiveness.

BACKGROUND: Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest. OBJECTIVE: To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar). METHODS: Fifteen asthmatic patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV1 [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 microg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure. RESULTS: The 2 formulations were equivalent in terms of predefined equivalence limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the 400-microg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant (P < .05) reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant (P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses (P < .05). CONCLUSIONS: Beclate and Qvar were equivalent for all primary and secondary outcome measures.     

Impact of PKU on the reproductive patterns in collaborative study families

Factors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class. Correlations found related to the question, "Is PKU the reason you don't want more children?" include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU. Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self-report, many clinics declare their counseling to be either "completely nondirective" or making a "conscious effort to be nondirective."     

Designs for Instruction, Designs for Change: Distributing Knowledge of Evidence-Based Practice

We comment on the target article by Weingardt (this issue), which discusses recent advances in instructional design and technology (IDT) and their implications for dissemination of evidence-based practices. These arguments are extended to the topic of psychological intervention design, and possibilities for new intervention structures are briefly explored. Finally, comments are offered on maintaining a careful balance between technological and social processes in the effort to promote the dissemination of innovative and evidence-based psychological procedures.     

Comparison of isolation media for recovery of Burkholderia cepacia complex from respiratory secretions of patients with cystic fibrosis

Burkholderia cepacia selective agar (BCSA) has previously been devised for isolation of B. cepacia from respiratory secretions of patients with cystic fibrosis and tested under research laboratory conditions. Here we describe a study in which BCSA, oxidation-fermentation polymyxin bacitracin lactose agar (OFPBL), and Pseudomonas cepacia agar (PCA) were compared in routine culture procedures for the ability to grow B. cepacia and inhibit other organisms. Three hundred twenty-eight specimens from 209 patients at two pediatric centers and 328 specimens from 109 adults were tested. Plates were inoculated, incubated, and read for quality and quantity of growth at 24, 48, and 72 h. Five (1.5%) specimens from 4 (1.9%) children and 75 (22.9%) specimens from 16 (14.7%) adults grew B. cepacia complex. At 24, 48, and 72 h, BCSA achieved 43, 93, and 100% detection, respectively; OFPBL achieved 26, 84, and 96%, respectively; and PCA achieved 33, 74, and 84% detection, respectively. Quality was assessed as pinpoint or good growth. At 24 h, most cultures growing B. cepacia complex had pinpoint colonies. By 48 and 72 h, 48 and 69% of B. cepacia complex cultures, respectively, had good growth on BCSA, while on OFPBL 19 and 30%, respectively, had good growth and on PCA 11 and 18%, respectively, had good growth. BCSA was superior to OFPBL and PCA in suppressing organisms other than B. cepacia complex; 40 non-B. cepacia complex organisms were isolated from BCSA, 263 were isolated from OFPBL, and 116 were isolated from PCA. We conclude that BCSA is superior to OFPBL and PCA in its ability to support the growth of B. cepacia complex and to suppress other respiratory organisms.     

Molecular analysis of <Emphasis Type="Italic">Fiji disease virus</Emphasis> genome segments 5, 6, 8 and 10

Summary. The complete sequences of Fiji disease virus (FDV) genome segments 5 (S5), S6, S8 and S10 were obtained and comprised 3150nt, 2831nt, 1959nt and 1819nt, respectively. Each segment contained a single ORF which encoded putative proteins of 115kDa, 97kDa, 69kDa and 63.0kDa, respectively. The putative amino acid sequences encoded by S5 and S6 contained putative leucine zipper motifs while FDV S5 and S8 each contained an ATP-GTP-binding motif. At the amino acid level, FDV S5, S6, S8 and S10 showed most similarity to the corresponding segments of Rice black-streaked dwarf virus. Based on sequence similarities, it is predicted that FDV S8 encodes a minor core protein, while FDV S10 encodes an outer capsid protein. The evolutionary relationships of FDV to other reoviruses are discussed.The nucleotide sequence data for FDV S5, S6, S8 and S10 are available in the DDBJ/EMBL/GenBank databases under the accession numbers AY029521, AF356083, AY297693 and AY297694, respectively.     

Mucin is produced by clara cells in the proximal airways of antigen-challenged mice

Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype of mouse airway mucous cells. In naive mice, ciliated (approximately 40%) and nonciliated (approximately 60%) epithelial cells line the airways, and > 95% of the nonciliated cells are Clara cells that contain Clara cell secretory protein (CCSP). Mucous cells comprise < 5% of the nonciliated cells. After sensitization and a single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive mucous cell numbers increase dramatically, appearing 6 h after challenge (21% of nonciliated/nonbasal cells), peaking from Days 1-7 (99%), and persisting at Day 28 (65%). Throughout the induction and resolution of mucous metaplasia, ciliated and Clara cell numbers identified immunohistochemically change only slightly. Intracellular mucin content peaks at Day 7, and mucin expression is limited specifically to a Clara cell subset in airway generations 2-4 that continue to express CCSP. Functionally, Clara cells are secretory cells that express the regulated exocytic marker Rab3D and, in antigen-challenged mice, rapidly secrete mucin in response to inhaled ATP in a dose-dependent manner. Thus, Clara cells show great plasticity in structure and secretory products, yet have molecular and functional continuity in their identity as specialized apical secretory cells.     

Screening for cognitive impairment in older African-Caribbeans

BACKGROUND: There are increasing numbers of older African-Caribbeans in the United Kingdom. Screening instruments are commonly used in the detection of cognitive impairment, but have not been assessed within this population. This study aimed to develop culturally modified versions of screening instruments for cognitive impairment (Mini-Mental State Examination (MMSE) and Abbreviated Mental Test (AMT)) and to determine their sensitivity and specificity in the diagnosis of dementia. METHODS: The instruments were modified using a process involving a community group of African-Caribbeans and an academic group of health professionals. They were used in a two-stage study involving community resident African-Caribbeans aged 60 years or over in inner-city Manchester, comparing the screening instruments against a computerized diagnostic interview. RESULTS: One hundred and thirty people completed the study. The results for the largest subgroup, the Jamaicans (N = 96) were analysed. Effects of gender, age and education on the MMSE and AMT scores were evaluated. The correlations between the screening instruments and diagnostic interview were highly significant (P < 0.001). At appropriate cut-offs both screening instruments demonstrated high sensitivity and acceptable specificity levels. CONCLUSIONS: A defined process with lay input has assisted in producing culturally modified versions of the MMSE and AMT that perform well compared with a diagnostic interview, if an appropriate cut-off is used. They are easy to administer and acceptable to older African-Caribbean people. The results need to be viewed within the limitations of the current study.     

Ultrastructural Morphometric Study of Follicular Center Lymphocytes: II. Analyses of Cleaved-Cell Populations Do Not Support the Lukes-Collins' Concept

Ultrastructural morphometric analysis was carried out on six cases of lymph node biopsies with reactive hyperplasia to establish the frequency and depth of invaginations in nuclear profiles situated in the mantle zones and follicular centers. The frequency distribution of the depth of invaginations was similar in nuclear profiles whether in the small lymphocytes of mantle zones or the small, partially transformed (centrocytes) and fully transformed (centroblasts) lymphocytes of follicular centers. Invaginated and cleaved lymphocytes were not confined to the partially transformed (centrocytic) lymphocytes of follicular centers, and nuclear profiles with invaginations bore no resemblance to those depicted in the Lukes-Collins model. A considerable proportion of mantle zone lymphocyte nuclear profiles had invaginations (ranging from 7.5% to 53.6%) and there was no difference between the frequency of deep indentations or clefts in mantle zone lymphocytes (8.1 ± 5.4%) and the small unstimulated (9.3 ± 5.3%) and partially transformed (8.4 ± 1.4%) lymphocytes in follicular centers. Computer modeling of stylized nuclei with conical indentations indicated that all lymphocytic nuclei likely have multiple invaginations or groove-like creases.     

Affective and Behavioral Stress Outcomes in Alzheimer's Caregivers

Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring.