Are there new biomarkers of the gastroduodenal microbiota useful in the diagnosis of coeliac disease in children? A pilot study.

The changing of microbiome could precede the development of coeliac disease (CeD). We compared the bacterial profile of microbiota of tissues collected simultaneously from the stomach and duodenum in newly diagnosed patients with CeD. Biopsies were collected from 60 children and adolescents aged 2-18 years: (1) 40 patients with CeD; (2) 20 children as control group. The evaluation of the bacterial microbiota was carried out by sequencing the V3-V4 regions of the 16S rRNA subunit, using next-generation sequencing (NGS). The composition of bacterial microbiota was correlated with clinical and blood parameters. The beta diversity analysis revealed a significant dissimilarity in the gastric samples between the CeD and control group (Bray-Curtis index, P = 0.008, and weighted UniFrac distance, P = 0.024). At L2 (phylum level), Campylobacterota was only present in the stomach of the CeD group. A comparison of the abundance of bacteria between the stomach and duodenum showed significant differences in 10 OTUs (operational taxonomic units) in the control and 9 OTUs in the CeD group at L6 (genus) and in 8 OTUs and in 6 OTUs, respectively, at L7 (species). A significant correlation was observed between the genus Novosphingobium in stomach of CeD group and possession of the DQ2.5 and DQ 8 allele, and in the duodenum - between the DQ 8 allele and the species Blautia wexlerae. Significant differences in selected, little-known genera of bacteria suggest their potential role as new biomarkers in the development of CeD. To fully understand the mechanism of CeD development in genetically predisposed individuals, it is necessary to take into account not only the abundance of a given genus or species of bacteria, but also the anatomical location of its occurrence.

Data processing tasks in wireless GI endoscopy: image-based capsule localization & navigation and video compression.

The paper addresses data processing support that is required in capsule gastrointestinal endoscopy. First, capsule position estimation method using standard MPEG-7 image features (descriptors) is discussed. The proposed approach makes use of vector quantization, principal component analysis and neural networks. Next, new algorithms dedicated for virtual colonoscopy (VC) human body inspection are described. The VC images can be registered with endoscopic ones and help in capsule localization and navigation. Finally, an original, low-complexity, efficient image compression method, based on integer-to-integer 4x4 DCT transform, is presented and experimentally verified.

Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland.

BACKGROUND: Acetylsalicylic acid (ASA) and other nonsteroid anti-inflammatory drugs (NSAIDs) are reported to account for 21-25% of all adverse drug reactions. Some asthmatics may react to ASA and other NSAIDs with acute bronchoconstriction, profuse rhinorrhea and skin flushing. This is a distinct clinical syndrome called aspirin-induced asthma (AIA). The prevalence of AIA among asthmatic patients in Poland has not been previously assessed. METHODS: A questionnaire survey of 12,970 adults of both sexes, randomly selected from the population of Poland. RESULTS: The prevalence of AIA in the general population of Poland was estimated as 0.6%. Thirty patients (4.3%; 95% CI: 2.8-5.8) of 703 asthmatics (5.4% of general population) reported symptoms attesting to hypersensitivity to aspirin. In 27% of them the reactions were precipitated by aspirin, whereas in the remaining subjects by other NSAIDs. CONCLUSIONS: The prevalence of AIA in Poland is 4.3%, being somewhat lower than in Finland and Australia, where it was recently reported to account for 8.8 and 10.9% of the adult asthmatics, respectively. These figures indicate that aspirin hypersensitivity might be a significant community problem.

Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma.

There is a subset of patients with bronchial asthma who are susceptible to disease exacerbation upon receiving aspirin and other nonsteroidal anti-inflammatory drugs. This is a clinical syndrome, called aspirin-induced asthma (AIA), associated with alterations in arachidonate metabolism and cysteinyl-leukotriene overproduction. The natural history and clinical characteristics of this type of asthma were studied. Sixteen clinical centres in 10 European countries provided standardized information to the specially developed patient-oriented database regarding: medical history, physical examination, diagnosis, and treatment. Diagnosis of AIA was based on a typical history, confirmed by positive aspirin provocation tests, carried out in 91% of the patients. A total of 500 patients were enrolled in the study. AIA developed according to a pattern, characterized by a sequence of symptoms. First, persistent rhinitis, appearing at a mean age of 29.7+/-12.5 yrs, then asthma, aspirin intolerance and nasal polyposis appear. The clinical presentation in different European countries was remarkably similar. In females, who outnumbered males by 2.3:1, the onset of symptoms occurred significantly earlier and the disease was more progressive and severe than in males. Atopy, present in approximately a third of patients, led to earlier manifestation of rhinitis and asthma, but not of aspirin intolerance or nasal polyposis. A family history of aspirin intolerance, recorded in 6% of patients, had a less evident effect on the course of the disease than sex or atopy. Fifty one per cent of patients, in addition to inhaled steroids, required chronic systemic corticosteroid therapy at a mean dose of 8 mg prednisone x day(-1). Surprisingly, 15% of patients were unaware of intolerance to aspirin and learnt about it only after having provocation tests performed. All over Europe, aspirin-induced asthma develops in a similar characteristic way. Its course is influenced by sex and the presence of atopy. In half of the patients, asthma is severe, and steroid-dependent. The uniform natural history of aspirin-induced asthma might suggest a common underlying principle.

Epidemiology and impact of rotavirus diarrhoea in Poland.

Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases). Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score > or =11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (+/-9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus gastroenteritis in Poland.

Intranasal fluticasone propionate for chronic eosinophilic rhinitis in patients with aspirin-induced asthma.

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia.

Recent evidence indicates that aspirin inhibits thrombin generation in clotting blood. We noticed that this effect was less pronounced in patients with hypercholesterolemia. The aim of the study was to prove this observation. The effects of aspirin on thrombin generation were evaluated in (1) 46 healthy volunteers, 2 hours after ingestion of a single, 500-mg dose and (2) 28 survivors of myocardial infarction who took 300 mg aspirin/d for 2 weeks. In both populations, two well-matched subgroups were distinguished, using a serum cholesterol level of 6.2 mmol/L (240 mg/dL) and an LDL cholesterol level of 4.0 mmol/L (155 mg/dL) as borderline. Thrombin generation was monitored ex vivo in blood emerging from a skin microvasculature injury and additionally, in a single-dose study in vitro in recalcified plasma. Aspirin depressed thrombin generation in the group of subjects with serum cholesterol < 6.2 mmol/L and LDL cholesterol < 4.0 mmol/L but not in the group with high blood cholesterol levels. Inhibitory effects of aspirin were more pronounced after the 2-week treatment than after a single dose. There was a significant correlation between total serum cholesterol or LDL cholesterol and total amount of thrombin generated after aspirin treatment. In subjects with high blood cholesterol levels, thrombin generation was not affected by aspirin. Blunting of aspirin action in hypercholesterolemia might be explained by (1) alterations in platelet lipid-protein matrix that render their membrane proteins less accessible for acetylation by aspirin and (2) changes in composition and structure of plasma lipoproteins that diminish the chance of aspirin to interact with prothrombin.

Autoimmune phenomena in bronchial asthma with special reference to aspirin intolerance.

We assessed the autoimmune status of 185 adult patients with bronchial asthma and 46 healthy subjects of similar sex and age. The patients were divided into groups with: (1) aspirin-induced asthma (AIA) (n = 80); (2) intrinsic asthma with good aspirin tolerance (n = 46); and (3) atopic asthma (n = 59). Antinuclear antibodies (ANA) at a titer of > or = 1:40 were present in the serum of 55% of the patients with AIA, 41% of those with intrinsic asthma, 39% of those with atopic asthma, and 11% of the healthy subjects, with the difference between each patient group and the healthy subjects being statistically significant (p < 0.05). The fluorescence staining pattern of ANA on Hep-2 cells was mainly speckled, but the precise antigen specificity of the antibodies could not be identified with reference sera against extractable nuclear antigens. None of the subjects exhibited anti-double stranded deoxyribonucleic acid (anti-ds-DNA) or anti-neurtrophil cytoplasmic antibodies (ANCA). Positive ANA were associated with signs of complement activation, the presence of rheumatoid factor, and circulating immune complexes. Clinical signs of autoimmunity, evidenced by rheumatic symptoms, cold sensitivity, and Raynaud's phenomenon, were more common among the patients who tested positively for ANA. The assessment of autoimmunity may help in better characterizing patients with asthma and understanding various symptoms of the disease. Any causal relationship between asthma and autoimmunity remains to be established.

[High levels of cholesterol and lipoprotein (A) in serum decreases the inhibitory effect of aspirin on generation of thrombin]. / Wysokipoziom cholesterolu i lipoproteiny (A) w surowicy zmniejsza hamujacy wplyw aspiryny na generacje trombiny.

Aspirin (ASA) is widely used in the treatment of cardiovascular diseases. Recently, we have found that aspirin decreases not only platelet aggregation but also thrombin generation. This effect, however, was seen only in certain subjects. Therefore we decided to examine influence of a single dose of aspirin (500 mg) on thrombin generation in healthy volunteers. Thrombin genesis was assessed by serial measurements of fibrinopeptide A concentration in blood emerging from standardised forearm skin incisions. Aspirin reduced thrombin generation in persons with normal serum level of lipids. This effect was lost, however, in subjects with high level of cholesterol and lipoprotein (a)--well known risk factors of ischaemic heart disease. While the mechanism by which aspirin affects thrombin generation remains to be elucidated, our data indicate that hypercholesterolemic subjects might benefit less than others from preventive aspirin treatment.

Interferon-gamma in the treatment of atopic dermatitis: influence on T-cell activation.

Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. Its pathogenesis remains obscure and its treatment difficult. We have studied the efficacy of systemic recombinant human interferon-gamma (rhIFN-gamma) treatment (0.05 mg/m2 sc on 3 consecutive days, during 4 weeks) in 10 patients with severe AD. Marked clinical improvement was observed starting from the third week of treatment. Erythema, dryness, and lichenification were the most responsive symptoms. Serum immunoglobulin E and IgG4 levels did not change during treatment. Blood eosinophil count decreased only transiently at the end of the first and second series of injections (days 4 and 11; P = 0.02). Patients with AD showed an increase in CD25-positive cells (11.0% vs 4.88%; P = 0.0001) as compared to 10 age-matched healthy controls. Moreover, in parallel with clinical improvement, a distinct decrease in CD25-positive lymphocytes was observed on days 32 and 50 (P = 0.002 and P = 0.006, respectively). We suggest that in AD the beneficial effect of rhIFN-gamma might be related to the inhibition of excessive T-cell activation, perhaps of the subpopulations, producing interleukin (IL)-4 and IL-5.

[Human recombinant interferon gamma in the treatment of atopic dermatitis]. / Ludzki rekombinowany interferon gamma w leczeniu atopowego zapalenia skóry.

Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. We have studied the efficacy of recombinant human interferon gamma (rhINF-gamma) administered subcutaneously at a dose of 0.05 mg/m2 in ten patients with severe AD. Patients were treated for 4 weeks. They have shown marked clinical improvement starting from the third week of treatment. The efficacy of the drug varied, with erythema, dryness and lichenification being the most responsive symptoms. There was no change in serum immunoglobulin E and IgG4 levels. Whole blood eosinophil count decreased only transiently and was accompanied by a tendency to lower values of serum eosinophil cationic protein. Patient with AD showed an increased expression of a T-cell surface activation marker CD 25 as compared to healthy controls. Moreover, clinical improvement was roughly paralleled by the decrease in this T-cell activation marker. We conclude that rhINF-gamma is a novel efficacious therapeutic approach in severe AD. We suggest that its primary action might be related to the inhibition of T-cell activation.

Thrombinogenesis and its pharmacological modulation in atherosclerosis.

Appearance of thrombin in circulating blood can be monitored in the clinical setting by measuring specific thrombin markers, such as fibrinopeptide A, thrombin-antithrombin III or prothrombin fragment 1 + 2. In myocardial infarction monitoring of thrombin activity is of growing clinical interest. High levels of thrombin markers indicate an increased risk to a patient with myocardial infarction. Persistent, high thrombin marker levels, despite heparin anticoagulation, point to ongoing thrombin generation that may necessitate more anticoagulation, increased antiplatelet treatment, angioplasty or, in the future, use of new antithrombotic drugs. Recently, new sensitive methods have been developed to study the reaction of thrombin generation in clotting blood. These methods permitted to demonstrate that, aspirin, contrary to several other antiplatelet drugs, delay the process of thrombin formation. Continuous dampening of thrombin formation by aspirin might be one of the mechanisms responsible for its prophylactic and therapeutic efficacy. Hypercholesterolemic subjects might profit less than others from this type of treatment, since aspirin dampening effects are not so evident in hypercholesterolemia.

[Should hemostatic factors be considered in the prevention of cardiovascular disease?]. / Czy czynniki hemostatyczne nalezy uwzgledniac w prewencji chorób ukladu krazenia?

The relationship between thrombosis and atherosclerosis has been already suggested in the middle of the last century. More recently, in 1976 a hypothesis has been put forward which emphasize the leading role of chronic injury to endothelial cells followed by platelet attachment and the release of platelet derived growth factors in pathogenesis of atherosclerosis. There is also a growing body of evidence that cytokines, thrombin and the fibrinolytic system are involved in the initiation and progression of atherosclerotic lesions. Lipoprotein (a) is emerging as a link between atherogenic role of lipids and the haemostatic system. At the same time epidemiological data are pointing at the possible role of fibrinogen, factor VII and plasminogen activator inhibitor-1 as risk factors for ischemic heart disease. Thrombus formation is also responsible for the majority of acute coronary syndromes. On the other hand aspirin and other antiplatelet drugs seem to protect from vascular complications of atherosclerosis. Than the question which rather arises is: what is the best antithrombotic strategy in patients with cardiovascular diseases?