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Background/Aims Intestinal metaplasia (IM) of the stomach is a precancerous condition that is often not visible during conventional endoscopy. Hence, we evaluated the utility of magnification endoscopy and methylene blue (MB) chromoendoscopy to detect IM. Methods We estimated the percentage of gastric mucosa surface staining with MB, mucosal pit pattern, and vessel visibility and correlated it with the presence of IM and the percentage of metaplastic cells in histology, similar to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage. Results IM was found in 25 of 33 (75.8%) patients and in 61 of 135 biopsies (45.2%). IM correlated with positive MB staining (p

Cel: Powikłania ze strony układu oddechowego stanowią główną przyczynę zgonów pacjentów z twardziną układową (TU). Tętniczenadciśnienie płucne i śródmiąższowa choroba płuc stanowią najistotniejszez nich. Pacjenci są jednak często zdiagnozowani dopierow późnym okresie choroby, dlatego też istotne jest opracowaniemetody diagnostycznej do wczesnego wykrywania tych powikłań.Celem pracy była ocena wpływu wysiłku fizycznego na zmiany parametrówoddechowych. Materiały i metody: Badania przeprowadzono wśród 32 pacjentów zezdiagnozowaną TU; 72% pacjentów miało postać ograniczoną TU,28% postać uogólnioną. Wykonywano pomiar zdolności dyfuzyjnejpłuc dla tlenku węgla (DLCO), natężonej pojemności życiowej (FVC),natężonej objętości wydechowej pierwszosekundowej (FEV1) orazcałkowitej pojemności płuc (TLC) w spoczynku oraz bezpośrednio pozakończeniu wysiłku fizycznego. Wyniki: Pod wpływem wysiłku fizycznego obserwowano wzrostDLCO od 59,7% do 68,1% wartości należnej (p < 0,005). Nie stwierdzononatomiast istotnych statystycznie zmian wartości FVC, FEV1oraz TLC. Wnioski: U chorych na TU zdolność dyfuzyjna płuc dla tlenku węglapo wysiłku fizycznym uległa istotnej statystycznie poprawiew porównaniu z wartościami spoczynkowymi. Związane jest toz koniecznością zapewnienia właściwego utlenowania krwi tętniczeji wynika m.in. ze zwiększenia pojemności łożyska naczyniowego.W klinicznej interpretacji wartości DLCO należy uwzględniać opróczstężenia hemoglobiny i objętości pęcherzykowej także wpływ wysiłkuoraz związane z nim zmiany wielkości objętości rzutu serca.

Wstęp: Zmiany chorobowe w przebiegu układowych chorób tkankiłącznej dotyczą wielu narządów. W układzie oddechowym prowadządo nadciśnienia płucnego, objawiającego się obniżeniemtolerancji wysiłku, suchym kaszlem i dusznością. Cel pracy: Próba oceny zmian wybranych parametrów czynnościowychukładu oddechowego w przebiegu twardziny układowej. Materiały i metody: Do badania zakwalifikowano 39 pacjentówspełniających kryteria rozpoznania twardziny układowej. Czasobserwacji wynosił 2–44 miesięcy. W tym czasie przynajmniejdwukrotnie przeprowadzano u chorych badania czynnościoweukładu oddechowego. Do analizy wybrano tylko niektóre parametryczynnościowe, takie jak: całkowita pojemność płuc – TLC, natężonapojemność życiowa – FVC, natężona pojemność wydechowapierwszosekundowa – FEV1, i zdolność dyfuzyjna płuc dla tlenkuwęgla mierzona metodą pojedynczego oddechu – DLCOc – skorygowanado aktualnej wartości hemoglobiny. Wyniki: Największe zmiany spośród wszystkich ocenianych parametrówzarejestrowano w zakresie DLCOc. Był to parametr, któryistotnie statystycznie zmieniał się w trakcie obserwacji. Już napoczątku obserwacji u większości badanych DLCO była obniżonaponiżej dolnej granicy normy, co świadczyło o stopniu zaawansowaniachoroby. Wnioski: Powtarzana ocena DLCO umożliwia określenie zaawansowaniai postępu choroby. Inne oceniane parametry mają mniejszeznaczenie praktyczne.

BACKGROUND: The increasing incidence of obesity and overweight among children and adolescents will be reflected by the imminent increase in the number of obese patients who require more definitive methods of treatment. There is great interest in new, safe, simple, nonsurgical procedures for weight loss.

Introduction and Objective. Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Therefore, the aim of the study was to determine whether CS increases the expression of K-Ras, and promotes the development of CP in mice exposed to repeated episodes of acute pancreatitis (AP). Materials and method. C57BL6/cmdb mice were exposed to CS or a sham treatment for 12 weeks. After one week of exposure, half of the animals from both groups were additionally subjected to repeated cerulein treatment (once a week, for 10 consecutive weeks) to mimic recurrent episodes of AP. Extension of pancreatic damage was determined histologically by H&E and Trichrome staining. The expression of K-Ras protein and downstream components (NF-κB, Cox-2, TGF-β) was evaluated by immunohistochemistry. Results. C57BL6/cmdb mice exposed to CS or cerulein alone did not develop any chronic pancreatic damage. However, concomitant treatment with both of these agents caused focal acinar atrophy, with slight intralobular and perivascular areas of fibrosis, and inflammatory cells infiltration resembling mild CP. Moreover, immunohistochemistry examinations revealed increased pancreatic expression of K-Ras and NF-κB only in mice treated both with CS and cerulein. Conclusions. CS promotes development of CP in mice exposed to repeated episodes of AP. This process may be, at least partially, related to increased expression of K-Ras and NF-κB protein. [ABSTRACT FROM AUTHOR]

Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines. [ABSTRACT FROM AUTHOR]

Summary: Background: According to international treatment guidelines, inhaled rapid-acting β2 agonists should be used for the control of symptoms in patients with asthma. We compared the efficacy and safety of an extrafine combination inhaler containing a corticosteroid (beclometasone) plus a rapid-onset, long-acting β2 agonist (formoterol) with a short-acting β2 agonist (salbutamol) as reliever strategies in patients taking beclometasone–formoterol combination as maintenance treatment. Methods: In a double-blind trial undertaken in 183 centres in 14 European countries over 48 weeks, patients (aged ≥18 years) with asthma that was not fully controlled, with a forced expiratory volume in 1 s (FEV1) of at least 60% predicted, had a 2-week run in. During this period, patients were treated with a combination of beclometasone 100 μg and formoterol 6 μg per one inhalation twice daily plus salbutamol 100 μg as required delivered by use of a pressurised metered-dose inhaler. They were then randomly assigned in a 1:1 ratio with a computer-generated randomisation list to receive beclometasone 100 μg plus formoterol 6 μg or salbutamol 100 μg as reliever in addition to maintenance with beclometasone 100 μg plus formoterol 6 μg twice daily. Primary outcome was the time to first severe exacerbation (admission to hospital or visit to emergency department, or use of systemic steroids for ≥3 consecutive days). Secondary outcomes were number of severe exacerbations (events per 100 patients per year), time to and number of mild exacerbations, additional exacerbation variables, lung function, symptom scores, and asthma control. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00861926. Findings: 1714 patients were randomly assigned to the as-needed beclometasone–formoterol (n=857) and as-needed salbutamol groups (n=857), and 1701 were analysed (852 and 849, respectively). 326 severe exacerbations were reported by 251 patients during the study, and 99 versus 152 patients had at least one exacerbation during the 48 weeks, respectively. Compared with beclometasone–formoterol plus salbutamol as needed, beclometasone–formoterol for both maintenance and reliever treatment significantly increased the time to first exacerbation (209 days vs 134 days) by 75 days, with a 36% reduction in risk (hazard ratio 0·64 [95% CI 0·49 to 0·82]; p=0·0005), and the estimated probability was 12% and 18%, respectively (p=0·0003). The number of days with mild asthma exacerbations was also lower with as-needed beclometasone–formoterol than with as-needed salbutamol (56·04 days per patient per year vs 65·11 days per patient per year; 0·86 [0·76 to 0·98]; p=0·021). From the run-in period to week 48, both treatments improved symptoms (mean change −1·59 [–1·94 to −1·25] in the as-needed beclometasone–formoterol group vs −1·44 [–1·78 to −1·10] in the as-needed salbutamol group, difference −0·15 [–0·60 to 0·30]; p=0·507), percentage of asthma control days (9·5% [7·3 to 11·8] vs 10·9% [8·7 to 13·1], respectively, −1·4 [–4·3 to 1·6]; p=0·359), use of reliever (–0·29 [–0·38 to −0·20] vs −0·27 [–0·36 to −0·19], respectively, −0·02 [–0·13 to 0·10]; p=0·794), and lung function (FEV1, 0·090 [0·060 to 0·120] vs 0·090 [0·060–0·120], respectively, 0·001 [–0·040 to 0·040]; p=0·969), and were well tolerated (patients with serious adverse events, 32 [4%] and 41 [5%], respectively). Interpretation: Our results lend support to the use of the combination of a single inhaled corticosteroid plus a rapid-onset, long-acting β2 agonist for maintenance and relief in patients with moderate to severe asthma and provide encouraging data for the formulation of beclometasone–formoterol for this use. Funding: Chiesi Farmaceutici. [ABSTRACT FROM AUTHOR]

Mutations in the trypsinogen gene (PRSS1) cause human hereditary pancreatitis. However, it is not clear how mutant forms of PRSS1 contribute to disease development. We studied the effects of expressing mutant forms of human PRSS1 in mice. We expressed forms of PRSS1 with and without the mutation encoding R122H (PRSS1R122H) specifically in pancreatic acinar cells under control of a full-length pancreatic elastase gene promoter. Mice that did not express these transgenes were used as controls. Mice were given injections of caerulein to induce acute pancreatitis or injections of lipopolysaccharide to induce chronic pancreatitis. Other groups of mice were fed ethanol or placed on a high-fat diet to induce pancreatitis. Pancreata were collected and analyzed by histology, immunoblots, real-time polymerase chain reaction, and immunohistochemistry. Trypsin enzymatic activity and chymotrypsin enzymatic activity were measured in pancreatic homogenates. Blood was collected and serum amylase activity was measured. Pancreata from mice expressing transgenes encoding PRSS1 or PRSS1R122H had focal areas of inflammation; these lesions were more prominent in mice that express PRSS1R122H. Pancreata from mice that express PRSS1 or PRSS1R122H had increased levels of heat shock protein 70 and nuclear factor (erythroid-derived 2)–like 2, and reduced levels of chymotrypsin C compared with control mice. Increased expression of PRSS1 or PRSS1R122H increased focal damage in pancreatic tissues and increased the severity of acute pancreatitis after caerulein injection. Administration of lipopolysaccharide exacerbated inflammation in mice that express PRSS1R122H compared to mice that express PRSS1 or control mice. Mice that express PRSS1R122H developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice. Pancreata from mice that express PRSS1R122H had more DNA damage, apoptosis, and collagen deposition and increased trypsin activity and infiltration by inflammatory cells than mice that express PRSS1 or control mice. Expression of a transgene encoding PRSS1R122H in mice promoted inflammation and increased the severity of pancreatitis compared with mice that express PRSS1 or control mice. These mice might be used as a model for human hereditary pancreatitis and can be studied to determine mechanisms of induction of pancreatitis by lipopolysaccharide, ethanol, or a high-fat diet. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms. We investigated how oncogenic KRAS regulates the expression of fibroblast growth factor 21, FGF21, a metabolic regulator that prevents obesity, and the effects of recombinant human FGF21 (rhFGF21) on pancreatic tumorigenesis. We performed immunohistochemical analyses of FGF21 levels in human pancreatic tissue arrays, comprising 59 PDAC specimens and 45 nontumor tissues. We also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells (Kras G12D/+ mice) and fElas CreERT mice (controls). Kras G12D/+ mice were placed on an HFD or regular chow diet (control) and given injections of rhFGF21 or vehicle; pancreata were collected and analyzed by histology, immunoblots, quantitative polymerase chain reaction, and immunohistochemistry. We measured markers of inflammation in the pancreas, liver, and adipose tissue. Activity of RAS was measured based on the amount of bound guanosine triphosphate. Pancreatic tissues of mice expressed high levels of FGF21 compared with liver tissues. FGF21 and its receptor proteins were expressed by acinar cells. Acinar cells that expressed Kras G12D/+ had significantly lower expression of Fgf21 messenger RNA compared with acinar cells from control mice, partly due to down-regulation of PPARG expression—a transcription factor that activates Fgf21 transcription. Pancreata from Kras G12D/+ mice on a control diet and given injections of rhFGF21 had reduced pancreatic inflammation, infiltration by immune cells, and acinar-to-ductal metaplasia compared with mice given injections of vehicle. HFD-fed Kras G12D/+ mice given injections of vehicle accumulated abdominal fat, developed extensive inflammation, pancreatic cysts, and high-grade pancreatic intraepithelial neoplasias (PanINs); half the mice developed PDAC with liver metastases. HFD-fed Kras G12D/+ mice given injections of rhFGF21 had reduced accumulation of abdominal fat and pancreatic triglycerides, fewer pancreatic cysts, reduced systemic and pancreatic markers of inflammation, fewer PanINs, and longer survival—only approximately 12% of the mice developed PDACs, and none of the mice had metastases. Pancreata from HFD-fed Kras G12D/+ mice given injections of rhFGF21 had lower levels of active RAS than from mice given vehicle. Normal acinar cells from mice and humans express high levels of FGF21. In mice, acinar expression of oncogenic KRAS significantly reduces FGF21 expression. When these mice are placed on an HFD, they develop extensive inflammation, pancreatic cysts, PanINs, and PDACs, which are reduced by injection of FGF21. FGF21 also reduces the guanosine triphosphate binding capacity of RAS. FGF21 might be used in the prevention or treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: There are many potential factors that can modulate bronchial reactivity, including exposure to allergens, viral infections, and medications. The aim of this study was to analyze the effect of grass pollination intensity on the bronchial reactivity in seasonal allergic rhinitis (SAR) patients subjected to subcutaneous allergenic immunotherapy (SCIT)., Material and Methods: This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of SAR, randomly assigned to desensitization by pre-seasonal or maintenance SCIT. Bronchial provocation challenge with histamine was performed before the onset of immunotherapy, and repeated three times after each pollen season covered by this study. Bronchial reactivity was analyzed with regard to grass pollination intensity in 2005-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 20 or 50 grains per 1 m(3))., Results: After 3 years of SCIT, a significant decrease in bronchial responsiveness was observed in the analyzed group as confirmed by an increase in PC20 FEV1 histamine values (p = 0.001). An inverse tendency was observed after 2 years of SCIT, however. This second year of SCIT corresponded to the 2007 season, when a significantly higher number of days with at least 50 grains of pollen per 1 m(3) of air was recorded., Conclusions: FLUCTUATIONS IN POLLINATION INTENSITY OBSERVED DURING CONSECUTIVE YEARS OF IMMUNOTHERAPY CAN INFLUENCE BRONCHIAL REACTIVITY IN PATIENTS SUBJECTED TO SCIT (ISRCTN REGISTER: ISRCTN 86562422).

Background: Concentration of nitric oxide in exhaled air (FeNO) was revealed to decrease as a result of immunotherapy. However, individuals who are exposed to environmental allergens are characterized by elevated values of FeNO. The aim of this study was to analyze the effects of subcutaneous immunotherapy (SCIT) on the dynamics of FeNO determined during consecutive pollination seasons., Methods: This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of seasonal allergic rhinitis, randomly assigned to desensitization by preseasonal or maintenance SCIT. FeNO was measured prior to and during each pollen season (November-January and May-July, respectively). The results were conferred to data on grass pollination intensity in 2006-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 50 grains per 1 m(3))., Results: Median content of FeNO in exhaled air was significantly higher in 2007 compared to 2006 and 2008 pollen seasons. During 2007 and 2008 pollen seasons, significant increase in FeNO was observed compared to the respective preseasonal values. Median number of days with air concentration of grass pollen ≥ 50 grains per 1 m(3) of air during 4 weeks preceding seasonal FeNO measurement was significantly higher in 2007, corresponding to higher FeNO value recorded during this pollen season. However, no significant correlation was observed between seasonal number of days with ≥ 50 grass pollen grains per 1 m(3) of air and FeNO in exhaled air (r=0.09, p=0.362)., Conclusions: Most seasonal allergic rhinitis patients show physiological levels of FeNO prior to the pollen seasons and a marked increase in this parameter, probably proportional to pollination intensity, is observed within the seasons. ISRCTN Registry: ISRCTN86562422.

Objective: Carcinoids are low-grade, slow growing malignant tumors in the bronchi usually producing symptoms secondary to bronchial obstruction. We describe a case of 25-year-old woman who was initially diagnosed with asthma., Method: Case report., Results: Because of exacerbation and unresponsiveness to proper asthma treatment she was referred to spirometry, which showed low values of forced expiratory volume in 1 second. The shape of inspiratory limb of flow volume curve suggested an obstruction in the main bronchus or in the trachea. Further bronchoscopy revealed a tumor of the right main bronchus with characteristic histological features for carcinoid., Conclusions: Both the inspiratory curve and the expiratory part of the flow-volume loop should be evaluated in patients being evaluated for asthma. If there are changes in the shape of the inspiratory limb suggesting an obstruction, CT and/or bronchoscopy should be considered.