Analytical and clinical performance of the fully-automated LIAISONXL calprotectin immunoassay from DiaSorin in IBD patients.

OBJECTIVES: Distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) based on clinical symptoms is often difficult. In this study we assessed the performance of the fully-automated calprotectin immunoassay from DiaSorin in IBD diagnosis and follow-up and compared it to the EliA calprotectin 2 immunoassay. DESIGN: and Methods: The calprotectin immunoassay from DiaSorin run on the LIAISONXL was analytically and clinically validated and compared to the EliA calprotectin 2 immunoassay from Thermo Fisher Scientific run on the ImmunoCAP250. Five patient groups were measured (n â€‹= â€‹303): IBD: ulcerative colitis (UC) and Crohn's disease (CD); non-IBD: IBS, other gastrointestinal diseases and controls (healthy patients with no gastrointestinal disease). RESULTS: The calprotectin immunoassay of DiaSorin showed good analytical performance with frozen samples. The presence of blood in the stool can interfere with the measurement of calprotectin. Patients suffering from IBD (UC or CD) showed significant higher concentrations of fecal calprotectin compared to controls (UC:710 â€‹± â€‹921 â€‹mg/kg; CD:967 â€‹± â€‹1243 â€‹mg/kg; controls:11±8 â€‹mg/kg) using DiaSorin's immunoassay. The remaining non-IBD groups showed no significant difference compared to controls. Follow-up patients (n â€‹= â€‹9) showed a significant decrease in fecal calprotectin after treatment. At 50 â€‹mg/kg cut-off value, the negative predictive value for DiaSorin's immunoassay was 96% and the positive predictive value 83% (sensitivity of 95% and specificity of 86%). CONCLUSIONS: The lack of standardization contributes to the numerical differences between the two methods, but the qualitative conclusions do not differ. DiaSorin's calprotectin immunoassay can be used both to distinguish between IBD and non-IBD patients as well as for follow-up of IBD patients.

Increased Discontinuation Rates of Anti-TNF Therapy in Elderly Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40-59 years/≥60 years]. METHODS: IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. RESULTS: A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40-59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40-59 1.21; p = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62-0.98, p = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. CONCLUSIONS: Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections.

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.

BACKGROUND: Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. METHODS: In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. RESULTS: Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. CONCLUSION: These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.

Smoking is Associated with Higher Disease-related Costs and Lower Health-related Quality of Life in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS: In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS: Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.

Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.

Fluctuation analysis of respiratory impedance waveform in asthmatic patients: effect of airway obstruction.

Fluctuation analysis has great potential to contribute to pulmonary clinical science and practice. We evaluated the relationship between asthma and the respiratory impedance recurrence period density entropy (RPDEnZrs) and the variability (SDZrs). A non-invasive and simple protocol for assessing respiratory mechanics during spontaneous breathing was used in a group of 74 subjects with various levels of airway obstruction. Airway obstruction resulted in a reduction in the RPDEnZrs that was significantly correlated with both spirometric indices of airway obstruction (R = 0.48, p < 0.0001) and mean respiratory impedance (R = -0.83, p < 0.0001). These results suggest that the impedance pattern becomes less complex in asthmatic patients, which may explain the reduction in respiratory systems' adaptability to daily life activities. Preliminary evaluations indicate that RPDEnZrs may contribute to the asthma diagnosis, presenting accuracies of 82 and 87 % in patients with moderate and severe airway obstruction, respectively. On the other hand, SDZrs increased with obstruction (p < 0.0001) and was inversely correlated with spirometric indices of obstruction (R = -0.42, p = 0.0003) and directly associated with mean impedance (R = 0.88, p < 0.0001). This analysis contributes to elucidate previous studies and identified respiratory changes in patients with moderate and severe obstruction with an adequate accuracy (85 and 87 %, respectively).

Diagnostic performance of the Forced Oscillation Technique in the detection of early respiratory changes in rheumatoid arthritis.

The objective of this study was to evaluate the clinical potential of the Forced Oscillation Technique (FOT) in the detection of the early alterations in respiratory mechanics of Rheumatoid Arthritis (RA) patients. A total of 36 individuals were analyzed, 18 healthy and 18 with RA. The clinical usefulness of the parameters was evaluated investigating sensibility (Se), specificity (Sp) and the area under the receiver operating characteristic curve (AUC). In the RA group, all the 3 studied parameters obtained high accuracy for clinical use (AUC>0.9), while in spirometric parameters, no parameter obtained appropriate accuracy for clinical use (AUC < 0.7). In conclusion, the parameters obtained by FOT presented adequate Se and Sp, indicating that this technique can be helpful in the evaluation of the early respiratory mechanical alterations in patients with RA.

Validation of the Forced Oscillation Technique in the diagnostic of respiratory changes in patients with silicosis.

Silicosis is a typical occupational respiratory disease characterized by irreversible alterations throughout the alveolar and interstitial structure. The objectives of this study were (1) investigate the potential of the Forced Oscillation Technique (FOT) in the analysis of the patients with silicosis, and (2) evaluate the ability of FOT to identify early alterations in the respiratory mechanics of these patients. Sixty-one volunteers were analyzed: 20 healthy subjects and 41 with silicosis; these, were divided into 4 groups according to spirometric results: normal spirometric exam (n = 11); mild obstruction (n = 20); moderate and severe obstruction (n = 10.). A significant (p〈0.0001) increase in total resistance (R0) and mean resistance (Rm) were observed, as well as a decrease in the dynamic compliance (p〈0.0003) and mean reactance (p〈0.000004). R0 and Rm obtained adequate accuracy for clinical use (>80%). FOT parameters adequately described the pathophysiological changes associated with silicosis and presented adequate accuracy for clinical use, indicating that this technique can be helpful in the evaluation respiratory mechanics in this disease.

[Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces]. / Behandeling van recidiverende Clostridium dificile-geassocieerde diarree met een suspensie van donorfeces.

OBJECTIVE: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces. DESIGN: Uncontrolled interventional study. METHOD: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy. RESULTS: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor. CONCLUSION: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment.

Seasonal variability of free amino acids in two marine bivalves, Macoma balthica and Mytilus spp., in relation to environmental and physiological factors.

The seasonal variability of the intracellular free amino acid (FAA) concentration was studied in 5 Macoma balthica populations and 7 Mytilus spp. populations along their European distribution. Because of the well known physiological role of FAA as organic osmolytes for salinity induced cell volume regulation in marine osmoconformers, FAA variations were compared in bivalve populations that were exposed to high vs. low intraannual salinity fluctuations. In general, seasonal FAA variations were more pronounced in M. balthica than in Mytilus spp. In both bivalve taxa from different locations in the Baltic Sea, highest FAA concentrations were found in autumn and winter and low FAA concentrations were measured in summer. Seasonal patterns were less pronounced in both taxa at locations with constant salinity conditions. In contrast to Baltic Sea populations, Atlantic and Mediterranean bivalves showed high FAA concentrations in summer and low values in winter, regardless of seasonal salinity fluctuations. Significant seasonal FAA variations at locations with constant salinity conditions showed that salinity appeared not to be the main factor in determining FAA concentrations. The seasonal patterns of the main FAA pool components, i.e. alanine, glycine and taurine, are discussed in the context of seasonal variations in environmental factors (salinity, temperature) and physiological state (glycogen content, reproductive stage).

Efeito da obesidade sobre as propriedades resistivas e reativas do sistema respiratório / Effect of obesity on the resistive and reactive properties of the respiratory system

A fim de avaliar uma possível relação entre a obesidade e as modificações nas propriedades resistivas e reativas do sistema respiratório e do potencial de oscilações forçadas no estudo da obesidade, mecânica oscilações foram avaliados em 25 saudáveis e 25 indivíduos obesos...

Efeito do envelhecimento sobre as propriedades resistivas e reativas do sistema respiratório / Effect of aging on the resistive and reactive properties of the respiratory system

Os sintomas respiratórios em idosos podem ser confundidos com modificações fisiológicas que introduz erros no processo de diagnóstico. Esta obra tem como objetivo investigar as modificações nas propriedades resistivas e reativas do sistema respiratório com o aumento da idade da técnica de oscilações forçadas...

Broncholithiasis and lithoptysis associated with silicosis.

A case of broncholithiasis associated with massive silicosis is reported, showing a rare aspect of parenchymal lesions generating broncholiths as well as the presence of recurrent lithoptysis, with subsequent regression of radiological lesions. Aetiological, clinical, physiopathological, and radiological aspects of the disease are discussed, demonstrating the importance of the use of computed tomography in diagnosis. The mineralogical analysis of expectorated fragments is also shown.

Endoscopic resection of a large Brunner's gland adenoma.

Brunner's gland adenoma is a rare benign tumour of the duodenum. Less than 150 cases have been reported in English literature. We report a 73-year-old woman presenting with upper gastrointestinal obstructive symptoms and melena. Duodenoscopy revealed a large pedunculated tumour in the bulbus duodeni. Endoscopic snare polypectomy was successfully performed. Histological examination revealed a Brunner's gland adenoma. The literature on Brunner's gland adenoma is reviewed.

Gatifloxacina oral no tratamento da exacerbaçäo aguda da bronquite crônica. Um estudo aberto, multicêntrico, näo comparativo, Fase III b / Oral gatifloxacin in the treatment of acute exacerbation of chronic bronchitis (AECB). An open-label multicenter noncomparative phase IIIb study

Avaliar a eficácia e a segurança da gatifloxacina, uma nova 8-metoxi-fluoroquinolona com amplo espectro de atividade, em pacientes com exacerbaçäo aguda de DPOC. Foram incluídos 50 pacientes näo internados com exacerbaçäo aguda de DPOC, em um estudo aberto, näo comparativo, multicêntrico. Quarenta e três tinham exacerbaçäo aguda do tipo I, de acordo com critérios propostos por Anthonisen. Gatifloxacina foi dada por via oral, 400 mg/dia, por 7-10 dias. O sucesso clínico entre os pacientes avaliáveis foi de 94 por cento. H. influenzae, S. pneumoniae e M. catarrhalis foram isolados 28 vezes em 21 pacientes, e foram erradicados em todos, exceto em um caso. Efeitos adversos ocorreram em 19 pacientes, mas resultaram em interrupçäo do tratamento em apenas dois casos. A gatifloxacina é eficaz e segura em exacerbaçöes agudas da bronquite crônica.

Bronchodilator activity of Mikania glomerata Sprengel on human bronchi and guinea-pig trachea.

The effects of aqueous extracts and hydro-alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascular smooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea-pig trachea. HAE extract induced a concentration-dependent relaxation on guinea-pig trachea pre-contracted with histamine (IC50 0.34 (0.29-0.39) mg mL(-1)), acetylcholine (IC50 0.72 (0.67-0.77) mg mL(-1)) or K+ (IC50 1.41 (1.18-1.64) mg mL(-1)) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26-0.42) mg mL(-1)). The dichloromethane fraction induced a concentration dependent relaxation in guinea-pig trachea precontracted with K+ (IC50 0.017 (0.012-0.022) mg mL(-1)). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothropsjararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.

Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi.

BACKGROUND: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. METHODS: Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. CONCLUSION: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.

Comparison of in-vitro development of embryos originating from either conventional in-vitro fertilization or intracytoplasmic sperm injection.

In this retrospective study on 1628 consecutive cycles performed during a period of 4 years, development in vitro is compared of embryos obtained after either conventional in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). At 39-42 h after insemination or injection, embryos obtained after ICSI were significantly (P < 0.01) further developed (mean cell number 3.48 +/- 0.03) as compared with those obtained after IVF (3.22 +/- 0.03), whereas after 63-66 h of in-vitro development this difference was no longer present (mean cell number 6.11 +/- 0.15 versus 6.09 +/- 0.13 respectively). Culture of surplus embryos obtained after IVF resulted in a significantly higher (P < 0.001) mean incidence of blastocyst formation per cycle as compared with the ICSI group (31.8 +/- 1.9 versus 23.0 +/- 1.4 respectively). Blastocysts from both groups consisted of comparable numbers of cells. Blastocyst formation was also significantly higher when embryos were cultured in groups (31.2 +/- 1.8) compared to single culture (23.1 +/- 1.5; P < 0.01), in human tubal fluid (HTF) medium (29.2 +/- 1.7) compared with IVF-50(TM) medium (24.2 +/- 1.6; P < 0.01), and when they were cultured under 5% O(2) (30.3 +/- 1.5) compared with 20% O(2) (21.7 +/- 1.7; P < 0.01). In all culture conditions used, the mean incidence of blastocyst formation per cycle showed comparable differences in favour of the IVF group as compared with the ICSI group.

Analysis of pulmonary microvasculature changes after photodynamic therapy delivered to distant sites.

Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxicity, by disruption of the microvasculature or by a combination of these effects. Although systemic effects after PDT of small tissue areas (< 1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have described animal death after high dose PDT to tumors on the hind limb of animals and hypothesized that a toxic shock syndrome caused by vasoactive agents released after PDT is responsible. Because one of the most vulnerable organs to toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber. The PDT treatment conditions (25 mg/kg Photofrin, 24 h, 150 J/cm2 630 nm, maximum area 6.28 cm2) were chosen that produce systemic toxicity and lethality in rats. Adhesion of leukocytes in the lung was monitored in vivo using anti-CD-13-labeled microspheres. The progression of pulmonary edema was assessed by monitoring the leakage of rhodamine-labeled albumin and by wet-to-dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated. These data indicate that lung edema and acute respiratory distress syndrome is not the cause of death in these animals and that the toxicity is related to other mechanisms including circulatory shock after extensive muscle damage.