Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral lichen planus.

BACKGROUND: Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE: The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. METHODS: Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-ß, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). RESULTS: Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. CONCLUSIONS: The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP.

Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, Th2-type inflammatory disease. Chemoattractant receptor-homologous molecule on Th2 cells (CRTH2) is a prostaglandin D(2) (PGD(2)) receptor, expressed by Th2 cells and other inflammatory cells, including eosinophils and basophils, that mediates chemotaxis and activation. OC000459 is a selective CRTH2 antagonist and would be expected to suppress eosinophilic tissue inflammation. The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE. METHODS: In this randomized, double-blind, placebo-controlled trial, 26 adult patients (m/f = 22/4; mean age 41 years, range 22-69 years) with active EoE, dependent or resistant to corticosteroids, were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, and via biomarkers. The primary end point was the reduction in esophageal eosinophil infiltration. RESULTS: After an 8-week OC000459 treatment, the esophageal eosinophil load decreased significantly, from 114.83 to 73.26 eosinophils per high-power field [(eos/hpf), P = 0.0256], whereas no reduction was observed with placebo (102.80-99.47 eos/hpf, P = 0.870). With OC000459, the physician's global assessment of disease activity improved from 7.13 to 5.18 (P = 0.035). OC000459 likewise reduced extracellular deposits of eosinophil peroxidase and tenascin C, the effects not seen with placebo. No serious adverse events were observed. CONCLUSIONS: An 8-week treatment with the CRTH2-antagonist, OC000459, exerts modest, but significant, anti-eosinophil and beneficial clinical effects in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE and is well tolerated.

[Sinusitis in HIV infection]. / Sinusitis bei HIV-Infektion.

Case notes of 722 HIV-infected patients who had died between March 1986 and August 1993 were analysed to evaluate the prevention and characteristic features of sinusitis associated with HIV infection. In 73 patients (10%) sinusitis had been diagnosed at least once on the basis of radiological or clear-cut clinical criteria. In addition, 15 patients with sinusitis were identified among those attending an HIV out-patient clinic. There were altogether 126 episodes of sinusitis in 88 patients (62 men, 26 women; mean age 33 [19-69] years). In 62 patients the CD4 lymphocyte count was under 100/microliters. The most commonly affected site was the maxillary sinuses. Patients with mirror formation had a significantly longer duration of illness than those without (P = 0.021). In 58 patients the symptoms of fever, headache and rhinitis were predominantly caused by the sinusitis, in 49 only partially so, and in 19 sinusitis was a chance diagnosis. In 10 of 49 attacks of sinusitis the concurrent disease (e.g. cerebral toxoplasmosis, malignant non-Hodgkin lymphoma) had not been recognized by the referring doctor. There were 1-5 recurrences over an observation period of 11.8 (0-72) months in 23 patients.-These findings show that sinusitis frequently occurs in HIV-infected patients, takes a protracted course and is difficult to distinguish from concomitant diseases by its clinical presentation. If symptoms persist, possible concurrent respiratory infection or CNS involvement must be looked for. Sinus needle aspiration is of decisive importance to ascertain the causative organism.

[Ovarian hyperstimulation syndrome]. / Das ovarielle Uberstimulationssyndrom.

The ovarian hyperstimulation syndrome is the most serious complication following ovulation induction. It is assuming greater clinical importance now that the indication for ovulation induction is no longer limited to anovulatory women but expands to other infertility problems. In its most severe manifestation the ovarian hyperstimulation syndrome consists of massive ovarian enlargement with multiple cysts, hemoconcentration, ascites, and pleural and pericardial effusion. There is no specific treatment and a reduction in the incidence of this iatrogenic syndrome can be achieved only by preventive measures.

The transition from drug use and crime to noninvolvement: a case study.

There is a paucity of research on the factors related to the process of change from involvement to noninvolvement in drug use and criminal activity. This paper presents a case study of one subject's life history, obtained from depth interviews, which reveals this process. For this subject, rehabilitation was facilitated by specific structural factors which interacted with and altered facilitated by specific structural factors which interacted with and altered personal values.