Psychometric evaluation of a patient-reported outcome measure in pancreatic exocrine insufficiency (PEI)

Background/objectives

Pancreatic exocrine insufficiency (PEI) is commonly caused by chronic pancreatitis (CP) or cystic fibrosis (CF). There are no PEI-specific patient-reported assessments of symptoms and impacts. The PEI Questionnaire (PEI-Q) was developed through qualitative research with PEI patients and expert clinical input. This study evaluated the psychometric properties of the PEI-Q.

Assessment of personal exposure to ozone in asthmatic children residing in Mexico City

OBJECTIVE: A study was conducted to evaluate personal ozone exposure (O3p) among asthmatic children residing in Mexico City. MATERIAL AND METHODS: A total of 158 children were recruited from December 1998 to April 2000. On average, three O3p measurements were obtained per child using passive badges. Time-activity patterns were recorded in a diary. Daily ambient ozone measurements (O3a) were obtained from the fixed station, according to children's residence. Levels of O3a and ozone, weighted by time spent in different micro-environments (O3w), were used as independent variables in order to model O3p concentrations using a mixed-effects model. RESULTS: Mean O3p was 7.8 ppb. The main variables in the model were: time spent indoors, distance between residence and fixed station, follow-up group, and two interaction terms (overall R(2)=0.50, p<0.05). CONCLUSIONS: The O3w concentrations can be used as a proxy for O3p, taking into account time-activity patterns and the place of residence of asthmatic Mexican children.     

Noise-Optimized Virtual Monoenergetic Dual-Energy CT Improves Diagnostic Accuracy for the Detection of Active Arterial Bleeding of the Abdomen

Purpose

To evaluate diagnostic accuracy of a noise-optimized virtual monoenergetic imaging (VMI+) reconstruction technique for detection of active arterial abdominal bleeding on dual-energy (DE) CT angiography compared with standard image reconstruction.

Inhibitors of Leishmania mexicana CRK3 cyclin-dependent kinase: chemical library screen and antileishmanial activity

The CRK3 cyclin-dependent kinase of Leishmania has been shown by genetic manipulation of the parasite to be essential for proliferation. We present data which demonstrate that chemical inhibition of CRK3 impairs the parasite's viability within macrophages, thus further validating CRK3 as a potential drug target. A microtiter plate-based histone H1 kinase assay was developed to screen CRK3 against a chemical library enriched for protein kinase inhibitors. Twenty-seven potent CRK3 inhibitors were discovered and screened against Leishmania donovani amastigotes in vitro. Sixteen of the CRK3 inhibitors displayed antileishmanial activity, with a 50% effective dose (ED50) of less than 10 microM. These compounds fell into four chemical classes: the 2,6,9-trisubstituted purines, including the C-2-alkynylated purines; the indirubins; the paullones; and derivatives of the nonspecific kinase inhibitor staurosporine. The paullones and staurosporine derivatives were toxic to macrophages. The 2,6,9-trisubstituted purines inhibited CRK3 in vitro, with 50% inhibitory concentrations ranging from high nanomolar to low micromolar concentrations. The most potent inhibitors of CRK3 (compounds 98/516 and 97/344) belonged to the indirubin class; the 50% inhibitory concentrations for these inhibitors were 16 and 47 nM, respectively, and the ED50s for these inhibitors were 5.8 and 7.6 microM, respectively. In culture, the indirubins caused growth arrest, a change in DNA content, and aberrant cell types, all consistent with the intracellular inhibition of a cyclin-dependent kinase and disruption of cell cycle control. Thus, use of chemical inhibitors supports genetic studies to confirm CRK3 as a validated drug target in Leishmania and provides pharmacophores for further drug development.     

Improvement of diagnostic accuracy and screening conditions with liquid-based cytology

The aim of this population-based study was to compare the histological follow-up diagnoses of cervicocytological neoplasia (dysplasia, carcinoma in situ and carcinoma) in conventional Papanicolaou (CP) smear and ThinPrep PapTest samples (TP).All cytological samples from the County of Funen, Denmark, in the periods 2000 (n = 34,832) and 2002 (n = 29,995) were included in the study. In 2000 and 2002, the specimens were CP and TP, respectively. The detection rate of > or = mild dysplasia was 0.8% in CP and 1.4% in TP, showing a 75% increase in TP when compared with CP (p < 0.001). Histological follow-up of > or = moderate dysplasia revealed a neoplastic lesion in 77.1% and 87.9% in CP and TP, respectively (P < 0.001).The present study indicates that the diagnostic accuracy of cervical cytology is improved with liquid-based cytology. In addition, we focus on the optimized cellular material that shows the diagnostic details very clearly to the microscopist and leads to radically improved screening conditions.     

Complement-mediated enhancement of HIV-1 neutralisation by anti-HLA antibodies derived from polytransfused patients

We have recently shown that 'alloimmune sera' derived from polytransfused patients (PTP sera) are able to recognise and neutralise HIV in vitro. In this study we try to identify the protein(s), which are recognised by the PTP sera and elucidate mechanisms responsible for the neutralising capacity of these sera. The PTP sera allowed immunoprecipitation (IP) of HLA class II molecules on HIV-infected cells. To detect a potential cross-reactivity of alloreactive antibodies (Ab) with the HIV envelope protein gp160 or its subunits gp120/gp41 and HLA proteins, ELISA and FACS analyses were performed. The lack of reactivity of the PTP sera against rsgp160 in ELISA or FACS analysis indicated that recognition of cells was independent of HIV infection. To clarify whether interaction of the PTP sera with target cells has any effect on the infection process, virus neutralisation assays were performed. Inhibition of HIV infection was observed only when virus was pre-incubated with the PTP sera. Complement enhanced neutralisation of HIV-1 significantly. This enhancement was not due to complement-mediated lysis, because pre-incubation of the target cells with PTP sera did not inhibit HIV replication. Therefore, the neutralising effect of the Ab was due to blocking of the viral attachment/fusion process and not to negative signalling after infection. Since steric hindrance is possible only when HLA and gp120/gp41 are in close vicinity, isolation of rafts and IP assays were performed. These experiments revealed that gp120 and MHC class II molecules are indeed co-localised. The close physical association of gp120/gp41 and HLA strongly supports a mechanism for neutralisation of HIV by anti-HLA-Ab based on steric hindrance.