Analysis of patient flows for orthopedic procedures using small area analysis in Switzerland

BACKGROUND: In general cantons regulate and control the Swiss health service system; patient flows within and between cantons are thereby partially disregarded. This paper develops an alternative spatial model, based upon the construction of orthopedic hospital service areas (HSAOs), and introduces indices for the analysis of patient streams in order to identify areas, irrespective of canton, with diverse characteristics, importance, needs, or demands. METHODS: HSAOs were constructed using orthopedic discharge data. Patient streams between the HSAOs were analysed by calculating three indices: the localization index (% local residents discharged locally), the netindex (the ratio of discharges of nonlocal incoming residents to outgoing local residents), and the market share index (% of local resident discharges of all discharges in local hospitals). RESULTS: The 85 orthopedic HSAOs show a median localization index of 60.8%, a market share index of 75.1%, and 30% of HSAOs have a positive netindex. Insurance class of bed, admission type, and patient age are partially but significantly associated with those indicators. A trend to more centrally provided health services can be observed not only in large urban HSAOs such as Geneva, Bern, Basel, and Zurich, but also in HSAOs in mountain sport areas such as Sion, Davos, or St.Moritz. Furthermore, elderly and emergency patients are more frequently treated locally than younger people or those having elective procedures. CONCLUSION: The division of Switzerland into HSAOs provides an alternative spatial model for analysing and describing patient streams for health service utilization. Because this small area model allows more in-depth analysis of patient streams both within and between cantons, it may improve support and planning of resource allocation of in-patient care in the Swiss healthcare system.

Folliculo-stellate cells of "true dendritic" type are involved in the inflammatory microenvironment of tumor immunosurveillance of pituitary adenomas

Folliculo-stellate cells are a nonendocrine, sustentacular-like complementary population of the anterior pituitary. They currently are considered as functionally and phenotypically heterogeneous, with one subpopulation of folliculo-stellate cells possibly representing resident adenohypophyseal macrophages. We took advantage of a limited T-cell mediated inflammatory reaction selectively involving tumor tissue in three cases of pituitary adenoma (2 prolactin cell adenomas, and 1 null cell adenoma) to test the hypothesis whether some folliculo-stellate cells within inflammatory foci would also assume monocytic/dendritic properties. Immunohistochemical double labeling for S-100 protein and the class II major histocompatibility antigen HLA-DR indeed showed several arborized cells to coexpress both epitopes. These were distributed both amidst adenomatous acini and along intratumoral vessels, and were morphologically undistinguishable from conventional folliculo-stellate cells. On the other hand, markers of follicular dendritic cells (CD21) and Langerhans' cells (CD1a) tested negative. Furthermore, no S-100/HLA-DR coexpressing folliculo-stellate cells were seen in either peritumoral parenchyma of the cases in point nor in control pituitary adenomas lacking inflammatory reaction. These findings suggest that a subset of folliculo-stellate cells may be induced by an appropriate local inflammatory microenvironment to assume a dendritic cell-like immunophenotype recognizable by their coexpression of S-100 protein and HLA-DR. By analogy with HLA-DR expressing cells in well-established extrapituitary inflammatory constellations, we speculate that folliculo-stellate cells with such immunophenotype may actually perform professional antigen presentation. A distinctly uncommon finding in pituitary adenomas, lymphocytic infiltrates may therefore be read as a manifestation of tumoral immunosurveillance.

Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway

In experimental bacterial meningitis, matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) contribute to brain damage. MMP-9 increases in cerebrospinal fluid (CSF) during bacterial meningitis and is associated with the brain damage that is a consequence of the disease. This study assesses the origin of MMP-9 in bacterial meningitis and how ROS modulate its activity. Rat brain-slice cultures and rat polymorphonuclear cells (PMNs) that had been challenged with capsule-deficient heat-inactivated Streptococcus pneumoniae R6 (hiR6) released MMP-9. Coincubation with either catalase, with the myeloperoxidase inhibitor azide, or with the hypochlorous acid scavenger methionine almost completely prevented activation, but not the release, of MMP-9, in supernatants of human PMNs stimulated with hiR6. Thus, in bacterial meningitis, both brain-resident cells and invading PMNs may act as sources of MMP-9, and stimulated PMNs may activate MMP-9 via an ROS-dependent pathway. MMP-9 activation by ROS may represent a target for therapeutic intervention in bacterial meningitis.

Learning styles vary among general surgery residents: analysis of 12 years of data

PURPOSE: Understanding the learning styles of individuals may assist in the tailoring of an educational program to optimize learning. General surgery faculty and residents have been characterized previously as having a tendency toward particular learning styles. We seek to understand better the learning styles of general surgery residents and differences that may exist within the population. METHODS: The Kolb Learning Style Inventory was administered yearly to general surgery residents at the University of Cincinnati from 1994 to 2006. This tool allows characterization of learning styles into 4 groups: converging, accommodating, assimilating, and diverging. The converging learning style involves education by actively solving problems. The accommodating learning style uses emotion and interpersonal relationships. The assimilating learning style learns by abstract logic. The diverging learning style learns best by observation. Chi-square analysis and analysis of variance were performed to determine significance. RESULTS: Surveys from 1994 to 2006 (91 residents, 325 responses) were analyzed. The prevalent learning style was converging (185, 57%), followed by assimilating (58, 18%), accommodating (44, 14%), and diverging (38, 12%). At the PGY 1 and 2 levels, male and female residents differed in learning style, with the accommodating learning style being relatively more frequent in women and assimilating learning style more frequent in men (Table 1, p < or = 0.001, chi-square test). Interestingly, learning style did not seem to change with advancing PGY level within the program, which suggests that individual learning styles may be constant throughout residency training. If a resident's learning style changed, it tended to be to converging. In addition, no relation exists between learning style and participation in dedicated basic science training or performance on the ABSIT/SBSE. CONCLUSIONS: Our data suggests that learning style differs between male and female general surgery residents but not with PGY level or ABSIT/SBSE performance. A greater understanding of individual learning styles may allow more refinement and tailoring of surgical programs.

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.

Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid

The vitamin A metabolite retinoic acid (RA) plays a fundamental role in cellular functions by activating nuclear receptors. Retinaldehyde dehydrogenase-II (RALDH2) creates localized RA gradients needed for proper embryonic development, but very little is known regarding its regulated expression in adults. Using a human ex vivo model of allergic inflammation by coincubating IgE receptor-activated mast cells (MCs) with blood basophils, we observed prominent induction of a protein that was identified as RALDH2 by mass spectroscopy. RALDH2 was selectively induced in basophils by MC-derived interleukin-3 (IL-3) involving PI3-kinase and NF-kappaB pathways. Importantly, neither constitutive nor inducible RALDH2 expression was detectable in any other human myeloid or lymphoid leukocyte, including dendritic cells. RA generated by RALDH2 in basophils modulates IL-3-induced gene expression in an autocrine manner, providing positive (CD25) as well as negative (granzyme B) regulation. It also acts in a paracrine fashion on T-helper cells promoting the expression of CD38 and alpha4/beta7 integrins. Furthermore, RA derived from IL-3-activated basophils provides a novel mechanism of Th2 polarization. Thus, RA must be viewed as a tightly controlled basophil-derived mediator with a high potential for regulating diverse functions of immune and resident cells in allergic diseases and other Th2-type immune responses.

Quantitative isolation of mouse and human intestinal intraepithelial lymphocytes by elutriation centrifugation

Intestinal intraepithelial lymphocytes (IEL) are specialized subsets of T cells with distinct functional capacities. While some IEL subsets are circulating, others such as CD8alphaalpha TCRalphabeta IEL are believed to represent non-circulating resident T cell subsets [Sim, G.K., Intraepithelial lymphocytes and the immune system. Adv. Immunol., 1995. 58: 297-343.]. Current methods to obtain enriched preparations of intraepithelial lymphocytes are mostly based on Percoll density gradient or magnetic bead-based technologies [Lundqvist, C., et al., Isolation of functionally active intraepithelial lymphocytes and enterocytes from human small and large intestine. J. Immunol. Methods, 1992. 152(2): 253-263.]. However, these techniques are hampered by a generally low yield of isolated cells, and potential artifacts due to the interference of the isolation procedure with subsequent functional assays, in particular, when antibodies against cell surface markers are required. Here we describe a new method for obtaining relatively pure populations of intestinal IEL (55-75%) at a high yield (>85%) by elutriation centrifugation. This technique is equally suited for the isolation and enrichment of intraepithelial lymphocytes of both mouse and human origin. Time requirements for fractionating cell suspensions by elutriation centrifugation are comparable to Percoll-, or MACS-based isolation procedures. Hence, the substantially higher yield and the consistent robust enrichment for intraepithelial lymphocytes, together with the gentle treatment of the cells during elutriation that does not interfere with subsequent functional assays, are important aspects that are in favor of using this elegant technology to obtain unmanipulated, unbiased populations of intestinal intraepithelial lymphocytes, and, if desired, also of pure epithelial cells.

T cell-mediated immunoregulation in the gastrointestinal tract

In the intestinal tract, only a single layer of epithelial cells separates innate and adaptive immune effector cells from a vast amount of antigens. Here, the immune system faces a considerable challenge in tolerating commensal flora and dietary antigens while preventing the dissemination of potential pathogens. Failure to tightly control immune reactions may result in detrimental inflammation. In this respect, 'conventional' regulatory CD4(+) T cells, including naturally occurring and adaptive CD4(+) CD25(+) Foxp3(+) T cells, Th3 and Tr1 cells, have recently been the focus of considerable attention. However, regulatory mechanisms in the intestinal mucosa are highly complex, including adaptations of nonhaematopoietic cells and innate immune cells as well as the presence of unconventional T cells with regulatory properties such as resident TCRgammadelta or TCRalphabeta CD8(+) intraepithelial lymphocytes. This review aims to summarize the currently available knowledge on conventional and unconventional regulatory T cell subsets (Tregs), with special emphasis on clinical data and the potential role or malfunctioning of Tregs in four major human gastrointestinal diseases, i.e. inflammatory bowel diseases, coeliac disease, food allergy and colorectal cancer. We conclude that the clinical data confirms some but not all of the findings derived from experimental animal models.

[ECG-gated chest CT angiography: value for atypical chest pain evaluation]

PURPOSE: The aim of this study was to evaluate ECG-gated whole chest CTA as a routine triage tool for patients with acute chest pain. MATERIAL AND METHODS: Whole chest CTA with retrospective ECG-gating was performed in 30 patients with acute atypical chest pain. The ten main segments of the coronary arteries, the pulmonary arteries, the aorta, and the myocardium (function, morphology) were independently analyzed by a resident and two senior radiologists. The inter-observer agreement between resident and senior radiologists was calculated. A final diagnosis was determined by consensus. RESULTS: Thirty patients were included. The coronary artery segments, myocardium and pulmonary arteries were considered analyzable in 84%, 90% and 97% of cases respectively. A final diagnosis for the cause of pain was retained in 19 patients: significant coronary artery stenosis (5), pulmonary embolus (5), aortic dissection (1), hypokinetic cardiomyopathy (2), lung parenchymal abnormalities (5), and hiatus hernia (1). Inter-observer agreement ranged from 0.76 to 1 between senior radiologists and from 0.76 to 1 between resident and senior radiologists. The average time of image interpretation ranged from 14 to 15 minutes. CONCLUSION: ECG-gated whole chest CT angiography appears as a promising tool for the evaluation of acute chest pain. Combined evaluation of appearance and function of the myocardium can reveal additional interesting information.

Virosomes can enter cells by non-phagocytic mechanisms

Phagocytosis of fine particles (1 mum) by macrophages is a ligand-receptor-mediated, actin-based process, whereas the entering of smaller particles (resident dendritic cells. Therefore, virosomes are promising vaccine candidates.

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells

The lack of effective therapies for end-stage lung disease validates the need for stem cell-based therapeutic approaches as alternative treatment options. In contrast with exogenous stem cell sources, the use of resident progenitor cells is advantageous considering the fact that the lung milieu is an ideal and familiar environment, thereby promoting the engraftment and differentiation of transplanted cells. Recent studies have shown the presence of multipotent 'mesenchymal stem cells' in the adult lung. The majority of these reports are, however, limited to animal models, and to date, there has been no report of a similar cell population in adult human lung parenchyma. Here, we show the identification of a population of primary human lung parenchyma (pHLP) mesenchymal stromal cells (MSCs) derived from intraoperative normal lung parenchyma biopsies. Surface and intracellular immunophenotyping by flow cytometry revealed that cultures do not contain alveolar type I epithelial cells or Clara cells, and are devoid of the following hematopoietic markers: CD34, CD45 and CXCR4. Cells show an expression pattern of surface antigens characteristic of MSCs, including CD73, CD166, CD105, CD90 and STRO-1. As per bone marrow MSCs, our pHLP cells have the ability to differentiate along the adipogenic, osteogenic and chondrogenic mesodermal lineages when cultured in the appropriate conditions. In addition, when placed in small airway growth media, pHLP cell cultures depict the expression of aquaporin 5 and Clara cell secretory protein, which is identified with that of alveolar type I epithelial cells and Clara cells, respectively, thereby exhibiting the capacity to potentially differentiate into airway epithelial cells. Further investigation of these resident cells may elucidate a therapeutic cell population capable of lung repair and/or regeneration.

Cell population, viability, and some key immunomodulatory molecules in different milk somatic cell samples in dairy cows

Immune cells in the milk are most important in combating pathogens that invade the mammary gland. This study investigated the immune competence and viability of somatic milk cells that are already resident in milk and udders free of infection. Cells were studied in freshly removed milk to simulate conditions in the udder. Effects of incubation, cell preparation, and immunological stimulation with 0.5 mug/ml lipopolysaccharide (LPS) from Escherichia coli were analysed. Viability and differential counts of milk cells between high and low somatic cell count (SCC) quarters, and cisternal and alveolar milk with and without LPS stimulation were compared. Incubation and preparation of cells caused a cell loss which further increased with time independently of SCC and milk fraction. The viability of these cells was stable until 3 h post incubation and decreased until 6 h. Cell populations differed between both investigations, but did not change during the course of the experiment. mRNA expression of immune and apoptosis factors of the cells, measured by qPCR, did not change substantially: mRNA expression of caspase 3, Toll like receptor 4, and GM-CSF did not change, whereas the expression of the death receptor Fas/APO-1 (CD95), lactoferrin and lysozyme was decreased at 6 h. Cyclooxygenase-2 and TNF-alpha mRNA expression were decreased after 6 h of LPS treatment. In comparison with other studies in vivo or in vitro (in cell culture), in this study where cells are studied ex vivo (removed from the udder but kept in their natural environment, the milk) resident milk cells seem to be more vulnerable, less viable, less able to respond to stimulation, and thus less immune competent compared with cells that have freshly migrated from blood into milk after pathogen stimulation. The cell viability and differential cell count differed between high- and low-SCC milk and between cisternal and alveolar milk depending on the individual cow. In conclusion, the results support the view that for a most effective defence against invading pathogens the mammary gland is reliant on the recruitment of fresh immune cells from the blood.

Evaluation of pet contact as a risk factor for carriage of multidrug-resistant staphylococci in nursing home residents

BACKGROUND Pets, often used as companionship and for psychological support in the therapy of nursing home residents, have been implicated as reservoirs for antibiotic-resistant bacteria. We investigated the importance of pets as reservoirs of multidrug-resistant (MDR) staphylococci in nursing homes. METHODS We assessed the carriage of MDR staphylococci in pets and in 2 groups of residents, those living in nursing homes with pets and those living without pet contacts. We collected demographic, health status, and human-pet contact data by means of questionnaires. We assessed potential bacteria transmission pathways by investigating physical resident-to-pet contact. RESULTS The observed prevalence of MDR staphylococci carriage was 84/229 (37%) in residents living with pets and 99/216 (46%) in those not living with pets (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.4-0.9). Active pet contact was associated with lower carriage of MDR staphylococci (aOR, 0.5; 95% CI, 0.4-0.8). Antibiotic treatment during the previous 3 months was associated with significantly increased risk for MDR carriage in residents (aOR, 3.1; 95% CI, 1.8-5.7). CONCLUSIONS We found no evidence that the previously reported benefits of pet contact are compromised by the increased risk of carriage of MDR staphylococci in residents associated with interaction with these animals in nursing homes. Thus, contact with pets, always under good hygiene standards, should be encouraged in these settings.

Heart failure gene therapy: the path to clinical practice

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

Falkland Island English

This chapter examines some of the grammatical variability and non-standardness found in the English of the Falkland Islands. The Falklands are an archipelago of over 700 islands located in the western South Atlantic Ocean, 480km off the east coast of Argentina. Although the population is small – around 3000 - the islands cover an area of over 12000km2 – slightly larger than Jamaica and half the size of Wales, making them, after Greenland, the most sparsely populated political entity in the world. In political terms, the Falklands are an Overseas Territory of the United Kingdom. In contrast to the rural isolated image that the Falklands perhaps conjure up, the community is, in demographic terms, an urban and diverse one. Over 85% of the population living in the capital Stanley. The 2006 census (Government of the Falkland Islands 2007: 6) shows that 55% of the population were not born on the Islands, with the largest migrant groups coming from the UK, St Helena (another British Overseas Territory, located in the eastern South Atlantic), Chile and Australia. It also highlighted the fact that people born in 62 different countries were resident on the islands at the time (Pascoe and Pepper 2008: 38). By way of a comparison, only Monaco and Andorra, in Europe, have a higher proportion of their populations made up of migrants. In addition to the local Falkland population, there is a large military presence on the islands at the Royal Airforce Base at Mount Pleasant, 50km south-west of Stanley. The Head of State is the monarch of the UK, who is represented on the islands by a governor. The democratically elected 11-member Legislative Assembly is responsible for day-to-day government of the islands. The Falklands are perhaps most famous because of their 74 day occupation by Argentina in 1982. It is not appropriate here to go into detail about the dispute between the UK and Argentina about the sovereignty of the Islands. What is undisputed is that there has been a continuous Anglophone speech community on the islands since the early 1830s, making it one of the most recently developed ‘Inner Circle’ (Kachru 1985) Englishes in the world. This chapter examines the grammatical characteristics of Falkland Island English, drawn from a transcribed corpus of over 500,000 words of informal conversational speech, collected by Andrea Sudbury both in Stanley and in ‘Camp’ (the local name for the rest of the islands) (see Sudbury 2000, 2001 for more details about the methods used in the survey).