Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.     

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral‐naïve patients

Objectives

The aim of the study was to determine whether the incidence of first‐line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort.

Methods

We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of ≥1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as ‘early’, 1997–1999; ‘intermediate’, 2000–2002; ‘recent’, 2003–2007) was associated with the probability of reaching the endpoints by a survival analysis.

Results

Overall, the 1‐year probability of discontinuation of ≥1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all‐reason change were comparable according to calendar period [2000–2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69–0.98; 2003–2007, ARH 0.94, 95% CI 0.76–1.16, vs. 1997–1999; global P‐value=0.08]. Patients who started HAART during the ‘recent’ period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51–0.89 vs. ‘early’ period). Patients who started in the ‘intermediate’ and ‘recent’ periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21–72.45, and ARH 37.97, 95% CI 7.56–190.64, vs. ‘early’ period, respectively).

Conclusions

It seems important to evaluate reason‐specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.     

Pancreatic necrosis: CT manifestations

Pancreatic necrosis is a potential sequela of acute pancreatitis, which pathologically represents a collection of devitalized tissue. Appropriate therapeutic planning requires definition of this irreversibly damaged gland, the presence of which is not consistently diagnosed on the basis of clinical and laboratory data. Over an 18-month period, 22 patients with pancreatic necrosis were studied by one or more computed tomographic (CT) examinations. Retrospective analysis showed the findings to vary with the developmental stage of the necrotizing process. During the acute phase, there was considerable morphologic overlap of necrosis and pancreatic phlegmon. Typical findings were seen in the subacute and chronic stages and included diffuse enlargement of the gland with largely decreased central density. A thick, smooth surrounding rim produced a characteristic saclike configuration. CT-guided aspiration for culture material was performed in four patients with suspected superinfection. Negative gram stain and culture results in two patients allowed surgery to be performed on a more elective basis.