Biomedical subjects

Christopher J Miller

Publications and source records attributed to Christopher J Miller.

42 records · Page 3Linked to original sources

PubMed2003

Effects of budesonide inhalation suspension compared with cromolyn sodium nebulizer solution on health status and caregiver quality of life in childhood asthma.

OBJECTIVE: To compare the effects of 2 nebulizable controller asthma medications on caregiver and pediatric quality of life. METHODS: In this 52-week, randomized trial, children aged 2 to 6 years with mild to moderate persistent asthma received budesonide inhalation suspension 0.5 mg (total daily dose) once or twice daily (n = 168) or cromolyn sodium nebulizer solution 20 mg 4 times daily (n = 167) for 8 weeks, with dosage adjustment thereafter at the investigators' discretion. The Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), Compliance/Caregiver Satisfaction Questionnaire (CCSQ), Modified Child Health Questionnaire-Parent Form 50 (CHQ-PF50), and Functional Status-II(R) (FS-II[R]) Questionnaire were administered at baseline and weeks 8, 28, and 52. Global assessments of ease of asthma management and child health status were obtained from caregivers and physicians at the end of the study. RESULTS: Improvements from baseline in domain-specific (activities and emotional function) and total PACQLQ scores were greater at each time point (weeks 8, 28, and 52) for caregivers of patients treated with budesonide compared with caregivers of patients receiving cromolyn sodium. Only the budesonide group met the criterion for a clinically important improvement (>or=0.5 unit change) in all PACQLQ domains by week 8, which was maintained at weeks 28 and 52. Moreover, improvements surpassed the criterion for moderate clinical importance (1.0 unit change) in all PACQLQ domains for the budesonide group, but this level of improvement was only achieved in the activities domain (at week 28) for the cromolyn sodium group. Based on the CCSQ, budesonide resulted in greater caregiver satisfaction, treatment convenience, ease of use, and compliance compared with cromolyn sodium. Thus, 90.7% of caregivers in the budesonide group were "completely or very satisfied" compared with 53.4% in the cromolyn sodium group. Over half (54.6%) of caregivers in the budesonide group rated budesonide "highly or very convenient" compared with 23% for cromolyn sodium; 77% rated budesonide "extremely or very easy" to use compared with 47% for cromolyn. Adherence with daily medication regimens was reported for 76% of children in the budesonide group compared with 57% in the cromolyn sodium group. Child health status, as indicated by mean FS-II(R) scores, showed improvements from baseline in both groups at weeks 8, 28, and 52. There was a trend for these improvements to be superior in the budesonide group. Additionally, budesonide was superior to cromolyn sodium in caregiver and physician global assessments. At the end of the study, 76% of caregivers of children receiving budesonide reported asthma management to be "a great deal easier" compared with the start of the study, and 74% rated the overall health status of their child as "much better now than 1 year ago." In contrast, only 29% and 37% of caregivers whose children received cromolyn sodium provided these respective ratings. CONCLUSIONS: Budesonide inhalation suspension improved the quality of life for caregivers of children with asthma. Caregivers of children treated with budesonide had significantly fewer limitations in daily activities and emotional functioning compared with caregivers of children treated with cromolyn sodium nebulizer solution. The improvements in caregiver quality of life occurred earlier with budesonide compared with cromolyn sodium. Only caregivers in the budesonide group had a clinically important mean change from baseline in all PACQLQ domains by week 8. These benefits were maintained at week 52. Children treated with budesonide inhalation suspension and cromolyn sodium experienced improvements in health status, assessed using the FS-II(R). The greatest differences between treatments were seen in the disease-specific portion of the FS-II(R), which relates impairments in functional status to the child's illness. Caregiver and physician global assessment indicated significantly better overall child health after 1 year of treatment with budesonide, supporting an improvement in health status. Clinical trials in children 4 to 16 years of age with asthma have demonstrated greater effectiveness of inhaled corticosteroids versus cromolyn sodium on several clinical measures of efficacy. Measures of asthma control in this study, reported in detail elsewhere [Leflein et al. Pediatrics 2002;109:866-872], also have shown greater improvements with budesonide therapy. Treatment with budesonide inhalation suspension resulted in a significantly lower mean rate of asthma exacerbations, significantly longer times to first asthma exacerbation, significantly longer times to first additional use of chronic asthma therapy, and significant improvements in asthma symptom scores and breakthrough medication use compared with cromolyn sodium therapy. Additionally, children receiving budesonide inhalation suspension experienced more symptom-free days and episode-free days compared with children receiving cromolyn sodium. Safety profiles were similar between the 2 treatment groups. Budesonide inhalation suspension was associated with significantly greater caregiver satisfaction, convenience, ease of use, and compliance compared with cromolyn sodium nebulizer solution. This greater caregiver satisfaction and quality of life may be related to the greater asthma control achieved in children treated with budesonide therapy compared with cromolyn sodium. In addition, the convenience of once- or twice-daily dosing with budesonide inhalation suspension, compared with 3- or 4-times-daily dosing of cromolyn sodium, may decrease caregiver burden and enhance the willingness of caregivers to adhere to treatment regimens prescribed for their young children with asthma. This effect on caregiver adherence could further improve treatment effectiveness. This is the first clinical trial comparing the effects of a nebulized corticosteroid with that of an alternative nebulized therapy on quality of life in young children with asthma and their families. Compared with nebulized cromolyn sodium, budesonide inhalation suspension not only provides better overall child health status and asthma management, but greater caregiver quality of life and greater caregiver satisfaction, convenience, ease of use, and compliance.

Administration, Inhalation↗

PubMed2003

Stinging nettle dermatitis.

The stinging nettle (Urtica dioica) is a common weed that can cause a wide range of cutaneous reactions. Contact with the hairs or spines on the stems and leaves of the stinging nettle causes the release of several biologically active substances. The released chemicals act to cause itching, dermatitis, and urticaria within moments of contact. Extracts from the stinging nettle may provide therapeutic value for some inflammatory medical conditions. There is no standard treatment for stinging nettle dermatitis.

Dermatitis, Allergic Contact↗

PubMed2002

CD4+ T cells and monocytes elicited by immunization of rhesus monkeys with antigen-pulsed dendritic cells control SIV replication.

Most HIV infections occur by transmission across mucosal surfaces, where dendritic cells (DCs) are the first cells to encounter the virus. Dendritic cells are specialized antigen-presenting cells critical for eliciting T cell-mediated immune responses. Delayed-type hypersensitivity (DTH) is a cellular immune response in some viral infections and it is mediated by CD4+ and/or CD8+ T cells. We hypothesized that a DTH response to HIV induced by antigen-pulsed DCs would protect against a mucosal exposure to the virus. In a small pilot experiment, six rhesus monkeys were immunized with autologous, antigen-pulsed DCs by the intradermal route and five of the monkeys were boosted with a second dose of DCs at 3 months. Antibody responses to SIV were detected in two of six vaccinated monkeys, lymphocyte-proliferative responses were detected in five of the six monkeys and cytotoxic T lymphocyte (CTL) responses were detected in four of the six monkeys. Using a novel in vitro assay of SIV replication in DCs cocultured with autologous CD4+ T cells and monocytes, suppression of viral replication was detected from five of the six monkeys at multiple time points before and after SIV challenge. Macaques were orally challenged with SIVmac239 at 1-3 months after the booster inoculation. Peak viral loads were similar to those of four naive animals but, compared with naive monkeys, declined at 6 months to levels 1 log(10) or more lower in monkeys that had been vaccinated and that had > or = 50% suppression of SIV replication in DCs. Optimizing this immunization strategy may result in a strong antiviral DTH response that could better control a mucosal lentiviral infection.

Animals↗

PubMed2002

The relationship between simian immunodeficiency virus RNA levels and the mRNA levels of alpha/beta interferons (IFN-alpha/beta) and IFN-alpha/beta-inducible Mx in lymphoid tissues of rhesus macaques during acute and chronic infection.

To define the role of alpha/beta interferons (IFN-alpha/beta) in simian immunodeficiency virus (SIV) infection, IFN-alpha and IFN-beta mRNA levels and mRNA levels of Mx, an antiviral effector molecule, were determined in lymphoid tissues of rhesus macaques infected with pathogenic SIV. IFN-alpha/beta responses were induced during the acute phase and persisted in various lymphoid tissues throughout the chronic phase of infection. IFN-alpha/beta responses were most consistent in tissues with high viral RNA levels; thus, IFN-alpha/beta responses were not generally associated with effective control of SIV replication. IFN-alpha/beta responses were differentially regulated in different lymphoid tissues and at different stages of infection. The most consistent IFN-alpha/beta responses in acute and chronic SIV infection were observed in peripheral lymph nodes. In the spleen, only a transient increase in IFN-alpha/beta mRNA levels during acute SIV infection was observed. Further, IFN-alpha and IFN-beta mRNA levels showed a tissue-specific expression pattern during the chronic, but not the acute, phase of infection. In the acute phase of infection, SIV RNA levels in lymphoid tissues of rhesus macaques correlated with mRNA levels of both IFN-alpha and IFN-beta, whereas during chronic SIV infection only increased IFN-alpha mRNA levels correlated with the level of virus replication in the same tissues. In lymphoid tissues of all SIV-infected monkeys, higher viral RNA levels were associated with increased Mx mRNA levels. We found no evidence that monkeys with increased Mx mRNA levels in lymphoid tissues had enhanced control of virus replication. In fact, Mx mRNA levels were associated with high viral RNA levels in lymphoid tissues of chronically infected animals.

Animals↗

PubMed2002

Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial.

OBJECTIVE: The availability of antiinflammatory asthma medications for infants and young children has been limited. The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma. METHODS: We conducted a randomized, parallel-group, 52-week, open-label study in 36 US clinical sites. Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication; 287 children (86%) completed the study. Patients received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed by dose titration at the investigator's discretion. The main outcome measure was the rate of asthma exacerbations over 52 weeks. Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy, asthma symptom scores, rescue medication use, and health care resource use. RESULTS: The budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per year compared with 2.41 (1.85) for the cromolyn group, significantly longer times to first exacerbation and first use of additional long-term asthma medication, greater improvements in asthma symptom scores, reduced use of rescue medication, and fewer urgent care visits. Both treatments were well tolerated. CONCLUSIONS: Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma. Both treatments were well tolerated with similar adverse event profiles.

Administration, Inhalation↗

PubMedDate not supplied

Anti-HIV and -SIV immunity in the vagina.

Most HIV infections worldwide are transmitted through heterosexual contact. In order to develop vaccination strategies, the basic biology of the immune system in female reproductive tract and the full range of vaginal immune responses that occur during natural HIV infection must be understood. The cervicovaginal mucosa contains a complete set of immune cells, including antigen-presenting cells, CD4+ and CD8+ T cells, and B cells. The CVS of HIV-infected women and SIV-infected female rhesus macaques contain variable levels of antiviral antibodies. Some of this variation is due to the effects of female ovarian hormone cycle. IgG antibodies make up the bulk of the antiviral antibody response. However, IgA antibodies are present at lower levels. HIV/SIV-specific CD8+ cytotoxic T lymphocytes are present in the cervicovaginal mucosa of infected women and rhesus macaques. A vaccine that can elicit strong antiviral immunity may provide protection for hetorosexual HIV-1 transmission.

AIDS Vaccines↗