Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.     

Treatment with a proton pump inhibitor improves glycaemic control in type 2 diabetic patients - a retrospective analysis

We retrospectively studied whether treatment with esomeprazole improved HbA?(c) levels in type 2 diabetic patients. We selected 21 patients who had been treated with esomeprazole for 11 ± 3 months and 21 controls. HbA?(c) levels decreased in the esomeprazole-treated group. Our data indicate that proton pump inhibitors may improve glycaemic control in type 2 diabetic patients.     

Effect of chitosan malate on viability and cytoskeletal structures morphology of Caco-2 cells

The aim of this work was to evaluate the effects of the treatment with chitosan malate (CM) on viability of Caco-2 cells and on the morphology and the integrity of their cytoskeletal structures (microtubules, microfilaments). Cytotoxicity of CM, both as a solution and as microparticles obtained by spray drying, was evaluated by using the reduction of MTT reagent; microtubule and microfilaments organization of Caco-2 cells treated with CM solution was examined with immunofluorescence techniques in monolayers fixed with the glutaraldehyde-borohydride method.CM as a solution displayed a concentration-dependent cytotoxicity towards Caco-2 cells, with viability percentages of 5 ± 2%, 7 ± 3% and 31 ± 15% at 15, 10 and 5 mg/mL, respectively, while at 2.5 mg/mL or less cell viability was 90% or higher. CM microparticles also produced a remarkable cytotoxic effect (cell viability 84 ± 17%, 16 ± 8% and 5 ± 6% after treatment with 1, 5 and 10 mg CM per well, respectively), resulting more toxic than CM solution.Microtubules pattern of Caco-2 cells, which is a network regularly arranged around the nucleus, appeared deeply modified by CM treatment in a concentration-dependent way, with progressive microtubule changes in length and spatial disposition and deposition of fluorescent aggregates at the periphery of the cells. Furthermore, after treatment with 5-15 mg/mL CM, remarkable alterations of actin organization were observed, with a progressive disruption of the network of stress fibers and the appearance of actin aggregates inside the cell cytoplasm.In conclusion, viability and the cytoskeletal pattern of Caco-2 cells are modified by treatment with CM at high concentrations, which might be locally reached in vivo after application of drug-loaded chitosan microparticles onto mucosal cells.     

Tracheotomy improves experiment success rate in mice during urethane anesthesia and stereotaxic surgery

Urethane anesthesia is frequently used for acute experiments on small rodents in physiology and neuroscience. Severe respiratory distress is a common side-effect of urethane anesthesia in many strains of mice. Associated complications interfere with completion of experiments, and as a consequence more animals must be sacrificed. During experiments with stereotaxic brain surgery, we found that intubation by means of tracheotomy is an efficient way to maintain patent airways in these animals. Artificial ventilation of the animals is not required. In this paper we describe a simple, fast and reliable method for intubation of mice in experiments that involve a stereotaxic instrument. The method proved considerably easier to learn and apply than conventional intubation through the oral route. The incidence of breathing problems decreased from 77% in untreated mice to 9% in those that underwent tracheotomy. In addition, the success rate for our acute electrophysiological experiments increased from 24 to 77%. We conclude that tracheotomy reduces the number of sacrificed animals, and saves time and labor.     

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.     

CD33+ CD14− Phenotype Is Characteristic of Multinuclear Osteoclast‐Like Cells in Giant Cell Tumor of Bone

Giant cell tumor of bone (GCTB) is a benign bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. GCTB is composed of uniformly distributed osteoclastic giant cells, thought to originate from the fusion of monocyte–macrophage lineage cells, in a background consisting of mononuclear rounded cells and spindle‐shaped cells. Several reports showed the specific expression of markers, such as CD14 on the mononuclear rounded cell population, however, lacking osteoclastic giant cells. Blood monocytes that were CD14+, CD33+, or CD14+/CD33+ have also been shown to be programmed as pre‐osteoclasts. The macrophage marker CD33 is expressed earlier than CD14 in macrophage maturation, whereas CD14 is expressed longer than CD33. The aim of this study was to investigate CD14/CD33 expression profiles in GCTB. Nineteen GCTB tumor samples of 19 patients were studied. Immunofluorescent analyses were performed with monoclonal antibodies against CD14, CD33, RANK, and CD51. To unambiguously further prove the expression of these molecules, quantitative RT‐PCR was used with subsequent sequencing of its products. All samples showed similar immunoreactivity profiles. The mononuclear rounded cell population was positive for RANK, CD51, CD14, and CD33. The osteoclastic giant cell population expressed RANK and CD51, as well as CD33, but was consistently negative for CD14 expression. The CD14 and CD33 profiles were confirmed by quantitative RT‐PCR. These RT‐PCR products were sequence verified. Osteoclasts in GCTB are the result of fusion of CD33‐expressing pre‐osteoclasts that further fuse with CD14+ mononuclear cells. Although these results reflect a static rather than a dynamic spectrum, we strongly believe that osteoclastogenesis seems not to be the exclusive result of fusion of intratumoral CD14+ mononuclear cells. Moreover, CD33‐modulated osteoclastogenesis opens up the possibility for novel therapeutic directions.     

Factors associated with physiotherapy provision in a population of elderly nursing home residents; a cross sectional study

Background

Evaluating collaborative community health promotion initiatives presents unique challenges, including engaging community members and other stakeholders in the evaluation process, and measuring the attainment of goals at the collective community level. Goal Attainment Scaling (GAS) is a versatile, under-utilized evaluation tool adaptable to a wide range of situations. GAS actively involves all partners in the evaluation process and has many benefits when used in community health settings.

Methods

The purpose of this paper is to describe the use of GAS as a potential means of measuring progress and outcomes in community health promotion and community development projects. GAS methodology was used in a local community of seniors (n = 2500; mean age = 76 ± 8.06 SD; 77% female, 23% male) to a) collaboratively set health promotion and community partnership goals and b) objectively measure the degree of achievement, over- or under-achievement of the established health promotion goals. Goal attainment was measured in a variety of areas including operationalizing a health promotion centre in a local mall, developing a sustainable mechanism for recruiting and training volunteers to operate the health promotion centre, and developing and implementing community health education programs. Goal attainment was evaluated at 3 monthly intervals for one year, then re-evaluated again at year 2.

Results

GAS was found to be a feasible and responsive method of measuring community health promotion and community development progress. All project goals were achieved at one year or sooner. The overall GAS score for the total health promotion project increased from 16.02 at baseline (sum of scale scores = -30, average scale score = -2) to 54.53 at one year (sum of scale scores = +4, average scale score = +0.27) showing project goals were achieved above the expected level. With GAS methodology an amalgamated score of 50 represents the achievement of goals at the expected level.

Conclusion

GAS provides a "participatory", flexible evaluation approach that involves community members, research partners and other stakeholders in the evaluation process. GAS was found to be "user-friendly" and readily understandable by seniors and other community partners not familiar with program evaluation.     

Recent trends in breast cancer incidence in US white women by county-level urban/rural and poverty status

Background  

Unprecedented declines in invasive breast cancer rates occurred in the United States between 2001 and 2004, particularly for estrogen receptor-positive tumors among non-Hispanic white women over 50 years. To understand the broader public health import of these reductions among previously unstudied populations, we utilized the largest available US cancer registry resource to describe age-adjusted invasive and in situ breast cancer incidence trends for non-Hispanic white women aged 50 to 74 years overall and by county-level rural/urban and poverty status.