Tiotropium in the treatment of patients with asthma.

BACKGROUND: Asthma is a chronic disease with a significant disease burden, and many patients fail to achieve disease control despite recommended medical therapy. Recent evidence suggests that there may be benefits to the use of the long-acting anticholinergic agent tiotropium in patients with asthma. METHODS: We performed a systematic review of the literature to determine the role of tiotropium in management of adult patients with asthma. RESULTS: In six studies, 1773 patients were randomized and 1057 received tiotropium as an intervention. The mean prebronchodilator forced expiratory volume in 1 second was 60.1%. All six studies reported a small but statistically significant improvement in spirometry when using tiotropium as compared with the control. Improvement was reported in patients with both moderate and severe asthma, patients uncontrolled on previous regimens, patients treated with low- to high-dose inhaled corticosteroids regimens, and patients treated with and without long-acting ß-agonist therapy. Five studies evaluated clinical outcomes with tiotropium with variable success rates. Although a large randomized trial demonstrated a reduction in the frequency of severe asthma exacerbation with tiotropium, there is insufficient evidence to support the argument that tiotropium therapy leads to improvements in asthma symptom measures, asthma control days, asthma-related quality-of-life-scores, or rescue inhaler use. CONCLUSIONS: There is strong evidence supporting improvement in spirometry and asthma exacerbations with tiotropium in patients with moderate and severe asthma; therefore, tiotropium may be an effective intervention in patients with asthma.

The role of 8-oxoguanine DNA glycosylase-1 in inflammation.

Many, if not all, environmental pollutants/chemicals and infectious agents increase intracellular levels of reactive oxygen species (ROS) at the site of exposure. ROS not only function as intracellular signaling entities, but also induce damage to cellular molecules including DNA. Among the several dozen ROS-induced DNA base lesions generated in the genome, 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most abundant because of guanine's lowest redox potential among DNA bases. In mammalian cells, 8-oxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair pathway (OGG1-BER). Accumulation of 8-oxoG in DNA has traditionally been associated with mutagenesis, as well as various human diseases and aging processes, while the free 8-oxoG base in body fluids is one of the best biomarkers of ongoing pathophysiological processes. In this review, we discuss the biological significance of the 8-oxoG base and particularly the role of OGG1-BER in the activation of small GTPases and changes in gene expression, including those that regulate pro-inflammatory chemokines/cytokines and cause inflammation.

Time trends and age-related etiologies of pediatric hydrocephalus: results of a groupwise analysis in a clinical cohort.

OBJECTIVE: The current study aimed at evaluating experience with pediatric hydrocephalus and reviewing time trends and age-related differences in etiology, management, and outcomes of pediatric hydrocephalus at a tertiary care center in a south Asian country. METHODS: We conducted a retrospective cohort study based on case note review of pediatric patients (age, 1 month to 15 years) with hydrocephalus managed at Aga Khan University Hospital Karachi, over an 18-year period (1988-2005). For analysis, the study period was divided into two epochs (period A, 1988-1996; period B, 1997-2005) and study population was divided into two age groups (0-12 months and 1-15 years). RESULTS: A total of 338 cases of pediatric hydrocephalus were identified. Most common etiology of pediatric hydrocephalus was meningitis (38.1%), followed by congenital hydrocephalus (20.4%) and brain tumors (8.3%). Shunt infection and blockage were seen in 38 (11.2%) and 54 (16.0%) children, respectively; 67 (19.8%) required shunt revision. Highest rates of shunt failure were seen in bacterial meningitis (35.3%) and aqueductal stenosis (29.2%). Neurological and/or cognitive deficits were observed more frequently in children under 1 year of age (P = 0.029). Duration of hospital stay in period A was significantly higher than in period B (P < 0.001). Mortality occurred in 38 (11.2%); it did not differ between two epochs and age groups (P = 0.059 and P = 0.865, respectively). Highest mortality was associated with intraventricular hemorrhage (23.1%) and brain tumors (21.4%). CONCLUSION: Despite recent advancements, hydrocephalus is still associated with high rate of shunt failure and mortality. Factors associated with poor outcome include younger age group and etiology of hydrocephalus.