Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy

Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.     

Polymorphisms in the gene encoding thymus-specific serine protease in the extended HLA complex: a potential candidate gene for autoimmune and HLA-associated diseases

Positive selection plays a role, together with negative selection, in the prevention of autoimmunity. Thymus-specific serine protease is highly expressed in the thymus and is believed to be involved in positive selection of T cells. The gene encoding thymus-specific serine protease (PRSS16) maps to the extended HLA complex, which harbours several genes predisposing for autoimmune diseases. Here we report the results of scanning the genetic region containing PRSS16 for polymorphisms. Twenty-two polymorphisms were identified, including one missense polymorphism, one deletion leading to elimination of five amino acids, as well as several SNPs in the promoter region.     

Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Analysis of the Expression of I-Ak-like Antigens in Murine Fetal and Adult Tissues with the Monoclonal Antibody 10–2.16

The expression of I-Ak antigens in normal C3H/FeJ adult and 15-day embryonic mice has been investigated by indirect immunofluorescence staining of tissue cryostat sections with the anti I-Ak antigen monoclonal antibody 10-2.16. In adult mice I-Ak antigens were expressed in Langerhans-like cells in the skin, epithelium of the gastrointestinal tract, endometrium, thymic reticuloepithelial cells, and several capillary endothelia. On the other hand, these antigens were not detected in Kupffer cells, alveolar macrophages, brain or mammary gland. In 15-day-old embryos the expression of Ia-like antigens was restricted to thymic reticuloepithelial cells, isolated spleen cells, and capillaries of the gastrointestinal tract.     

CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8⁺ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8⁺ cells in a group of LTNP patients who had stable CD4⁺ cell counts (>500/mm³) for at least 7 years. Their CD8⁺ absolute numbers were similar to a control group composed of HIV-1⁺ patients who have a progressive decline of their CD4⁺ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28⁺, CD95 strongly positive CD8⁺ population, while disease progression is marked by the CD28⁻CD95⁺CD8⁺ subset. Purified CD8⁺ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-γ) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8⁺ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8⁺ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8⁺ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8⁺ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.     

Ventricular tachycardia as a complication of annular subvalvular ventricular aneurysm in a Caucasian woman

A Caucasian female patient with repetitive attacks of ventriculartachycardia and fibrillation caused by annular submitral leftventricular aneurysm is reported. During a follow-up periodof six years after aneurysmectomy, the patient remained symptom-free.     

In Situ Study of Haemopoiesis in Human Fetal Liver

The anatomy of haemopoietic cells in human fetal liver was examined using immunohistological techniques on frozen sections of 31 fetuses (10-28 weeks gestational age). The immunohistological findings were consistent with reported cell suspension data. With regard to the location of haemopoietic activity no particular relationship existed between the various haemopoietic cell lineages. A large number of proliferating cells was present; only a few of these were reactive with haemopoietic progenitor cell monoclonal antibodies (MoAb) CD34. A population of haemopoietic cells expressed CD43 antigen (MoAb MT1) alone or together with anti-vimentin MoAb reactivity; this population needs further delineation. Erythropoiesis and myelopoiesis occurred in clusters around sinusoids and portal triad vessels respectively. Lack of MoAb reacting exclusively with early developmental stages of erythropoiesis and myelopoiesis precluded dissection of these lineages. Lymphopoiesis occurred in a loosely scattered pattern without any sign of focal development. Pre-B and B-cell numbers increased with gestational age. Cells expressing markers of more mature B cells (surface IgD, CD35, and CD21) were rare. Also, few cells reacted with mature T-cell markers, but CD7+ cells were obviously present. This expression of CD7 on haemopoietic fetal liver cells suggests that T-cell precursors develop in fetal liver as well as B cells.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Diabetes and its Long-term Complications in General Practice: a Survey in a Well-defined Population

The aim of this study was to assess the prevalence of long-termcomplications in all patients with non-insulin-dependent diabetesmellitus, who were known to their general practitioners (GPs).During one year 19 GPs in the area of Hoogeveen in the Netherlandsexamined their non-insulin-dependent (NIDDM) patients, includingthose under specialist's care. A detailed protocol was used;the GPs were trained in the diagnostic procedures. Complicationswere either already known from the records or newly discoveredduring screening. In a population of 41940 14.5/1000 patientswith diabetes were identified: 12/1000 NIDDM and 2.5/1000 insulin-dependent-diabetesmellitus (IDDM). Of the 509 NIDDM patients, 387 (76%) couldbe screened for late complications. Signs and symptoms of latecomplications were found in many patients: retinopathy (14%),nephropathy (57%), neuropathy (68%) and macroangiopathy (53%).The prevalence of serious complications was: proliferative retino-and maculopathy (3.3%); diabetic foot (2.6%); renal failure(2.5%). The systemic screening revealed a high number of previouslyunknown cases. It is concluded that many patients with NIDDMdevelop signs and symptoms of late complications. Most casesare identified by systemic screening only. More long-term studiesof the prognosis of late com plications in NIDDM are needed.