Complicaciones relacionadas a la contención fija en ortodoncia:"Efecto giro". Revisión Bibliográfica

Las contenciones fijas en ortodoncia han demostrado tener excelentes resultados para la estabilidad y durabilidad del tratamiento. A pesar de esto, se ha observado que existen ciertos movimientos dentarios indeseados totalmente diferentes a una recidiva a su posición inicial previa al tratamiento de ortodoncia. El llamado "efecto giro" es uno de ellos, y se caracteriza por ser una inclinación en sentidos opuestos de los caninos contralaterales, en donde uno presenta una inclinación hacia vestibular y el otro hacia lingual o palatino. Se presenta principalmente en la mandíbula, a pesar de que la contención permanece perfectamente adherida a los dientes. El objetivo de esta revisión bibliográfica es evaluar los distintos factores reportados en la literatura que puedan estar relacionados con la aparición del "efecto giro" y qué tan relevantes pueden ser en su desarrollo. Como conclusión es importante considerar el carácter multifactorial de este tipo de complicaciones, en donde el tipo y calidad del alambre que se utilice para la contención, junto con las características periodontales del paciente demostraron tener cierta participación en la génesis de este, por lo tanto, resulta fundamental concientizar a los pacientes de la importancia de los controles ortodóncicos periódicos posteriores al retiro de los aparatos fijos para monitorear y controlar los resultados oclusales logrados y el estado de los dispositivos de contención instalados.

As contenções fixas em ortodontia têm demonstrado excelentes resultados para a estabilidade e durabilidade do tratamento. Apesar disso, observou-se que existem certos movimentos dentários indesejados totalmente diferentes de uma recorrência à sua posição inicial anterior ao tratamento ortodôntico. O chamado "efeito de torção" é um deles, e se caracteriza por uma inclinação em sentidos opostos dos caninos contralaterais, onde um apresenta uma inclinação para vestibular e outro para lingual ou palatino. Ocorre principalmente na mandíbula, apesar do retentor permanecer perfeitamente preso aos dentes. O objetivo desta revisão bibliográfica é avaliar os diferentes fatores relatados na literatura que podem estar relacionados ao aparecimento do "efeito turn" e quão relevantes podem ser no seu desenvolvimento. Em conclusão, é importante considerar a natureza multifatorial deste tipo de complicações, onde o tipo e a qualidade do fio utilizado para contenção, juntamente com as características periodontais do paciente, mostraram algum envolvimento na sua génese, pelo que é essencial conscientizar os pacientes sobre a importância de check-ups ortodônticos periódicos após a remoção dos aparelhos fixos para monitorar e controlar os resultados oclusais alcançados e o estado dos dispositivos de contenção instalados.

[Highlights of pancreatic surgery: extended indications in pancreatic neuroendocrine tumors]. / Highlights der Pankreaschirurgie: erweiterte Indikationen bei neuroendokrinen Tumoren des Pankreas.

Advanced pancreatic neuroendocrine tumors (paNET) are mostly characterized by infiltration of vascular structures and/or neighboring organs. The indications for resection in these cases should be measured based on the possibility of an R0 resection. Although the data situation for this rare entity is limited, small case series have shown a significant survival advantage in patients who underwent a radical resection in locally advanced stages of paNET. Both vascular reconstruction and multivisceral resection, when performed at experienced centers, should be considered as curative treatment options. The very special biological behavior of the paNET and the often young patient age justify a much more aggressive approach compared to the pancreatic ductal adenocarcinoma.

Short-term preoperative drainage is associated with improved postoperative outcomes compared to that of long-term biliary drainage in pancreatic surgery.

PURPOSE: The treatment of choice for patients presenting with obstructive cholestasis due to periampullary carcinoma is oncologic resection without preoperative biliary drainage (PBD). However, resection without PBD becomes virtually impossible in patients with obstructive cholangitis or severely impaired liver cell function. The appropriate duration of drainage by PBD has not yet been defined for these patients. METHODS: A retrospective analysis was conducted on 170 patients scheduled for pancreatic resection following biliary drainage between January 2012 and June 2018 at the University Hospital Dresden in Germany. All patients were deemed eligible for inclusion, regardless of the underlying disease entity. The primary endpoint analysis was defined as the overall morbidity (according to the Clavien-Dindo classification). Secondary endpoints were the in-hospital mortality and malignancy adjusted overall and recurrence-free survival rates. RESULTS: A total of 170 patients were included, of which 45 (26.5%) and 125 (73.5%) were assigned to the short-term (< 4 weeks) and long-term (≥ 4 weeks) preoperative drainage groups, respectively. Surgical complications (Clavien-Dindo classification > 2) occurred in 80 (47.1%) patients, with significantly fewer complications observed in the short-term drainage group (31.1% vs. 52%; p = 0.02). We found that long-term preoperative drainage (unadjusted OR, 3.386; 95% CI, 1.507-7.606; p < 0.01) and periampullary carcinoma (unadjusted OR, 5.519; 95% CI, 1.722-17.685; p-value < 0.01) were independent risk factors for postoperative morbidity, based on the results of a multivariate regression model. The adjusted overall and recurrence-free survival did not differ between the groups (p = 0.12). CONCLUSION: PBD in patients scheduled for pancreatic surgery is associated with substantial perioperative morbidity. Our results indicate that patients who have undergone PBD should be operated on within 4 weeks after drainage.

Perioperative Blood Management of Preoperative Anemia Determines Long-Term Outcome in Patients with Pancreatic Surgery.

BACKGROUND/PURPOSE: Anemia affects the postoperative course of patients undergoing a major surgical procedure. However, it remains unclear whether anemia has a different impact on the long-term outcome of patients with malignant or benign pancreatic disease. METHODS: A retrospective analysis of patients undergoing pancreatic surgery for pancreatic malignancies or chronic pancreatitis was conducted between January 2012 and June 2018 at the University Hospital Dresden, Germany. The occurrence of preoperative anemia and the administration of pre-, intra-, and postoperative blood transfusions were correlated with postoperative complications and survival data by uni- and multivariate analysis. RESULTS: A total of 682 patients were included with 482 (70.7%) undergoing surgical procedures for pancreatic malignancies. Univariate regression analysis confirmed preoperative anemia as a risk factor for postoperative complications > grade 2 according to the Clavien-Dindo classification. Multivariate regression analyses indicated postoperative blood transfusion as an independent risk factor for postoperative complications in patients with a benign (OR 20.5; p value < 0.001) and a malignant pancreatic lesion (OR 4.7; p value < 0.01). Univariate and multivariate analysis revealed preoperative anemia and pre-, intra-, and postoperative blood transfusions as independent prognostic factors for shorter overall survival in benign and malignant patients (p value < 0.001-0.01). CONCLUSION: Preoperative anemia is a prevalent, independent, and adjustable factor in pancreatic surgery, which poses a significant risk for postoperative complications irrespective of the entity of the underlying disease. It should therefore be understood as an adjustable factor rather than an indicator of underlying disease severity.

Simple Wound Irrigation in the Postoperative Treatment for Surgically Drained Spontaneous Soft Tissue Abscesses: A Prospective, Randomized Controlled Trial.

BACKGROUND: Soft tissue abscesses are among the most frequently encountered medical problems treated by different surgeons. Standard therapy remains incision and drainage with sterile saline irrigation during postoperative wound healing period. Aim of this prospective randomized controlled trial was to compare sterile irrigation versus nonsterile irrigation. STUDY DESIGN: A single center randomized controlled trial was performed to investigate postoperative wound irrigation. The control group used sterile irrigation, and the intervention group used nonsterile irrigation. Primary endpoints were reinfection and reintervention rates, assessed during follow-up controls for up to 2 years. Secondary endpoints were the duration of wound healing, inability to work, pain and quality of life. RESULTS: Between 04/2016 and 05/2017, 118 patients were randomized into two groups, with 61 allocated to the control- and 57 to the intervention group. Reinfection occurred in a total of 4 cases (6.6%) in the sterile protocol and 4 (7%) in the nonsterile protocol. Quality of life and pain values were comparable during the wound healing period, and patients treated according to the nonsterile irrigation protocol used significantly fewer wound care service teams. Despite equal wound persistence rates, a substantially shorter amount of time off from work was reported in the nonsterile protocol group (p value 0.086). CONCLUSION: This prospective, randomized trial indicates that a nonsterile irrigation protocol for patients operated on for soft tissue abscesses is not inferior to the standard sterile protocol. Moreover, a nonsterile irrigation protocol leads to a shorter period of inability to work with comparable pain and quality of life scores during the wound healing period.

SLC6A2 and SLC6A4 variants interact with venlafaxine serum concentrations to influence therapy outcome.

OBJECTIVE: The effects of genetic variants in genes encoding the target structures of antidepressants on the therapeutic efficacy of antidepressant drugs have been investigated with unconclusive results. One possible confounding factor in most studies was the fact that drug serum concentrations had not been determined. METHODS: Within a clinical setting, 56 inpatients suffering from depressive episodes in the context of either major depressive disorder or bipolar affective disorder were studied. Response to venlafaxine was assessed after 4 weeks of treatment and correlated to serum concentration and functional variants in genes encoding the norepinephrine (SLC6A2; rs28386840) and the serotonin transporter (SLC6A4; [5-HTTLPR], rs25531). Symptom change was evaluated using the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: No association between therapeutic response, venlafaxine serum concentration (active moiety) and rs28386840 was found. In carriers of the high expressing SLC6A4 genotype (lAlA-), a poor response to venlafaxine was found significantly more often. In subsamples stratified for serum concentration this held true for patients with serum concentrations between 201 and 400 ng/mL (n=21), while in patients with sub- (≤ 200 ng/mL; n=12) and supra-recommended (> 400 ng/mL; n=23) concentrations, no significant differences were observed. DISCUSSION: The observed association is consistent with findings of some previous studies, whereas others showed differing results highlighting the need for further investigations.

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis.

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia.

Compositional divergence and convergence in arbuscular mycorrhizal fungal communities.

In spite of the controversy that they have generated, neutral models provide ecologists with powerful tools for creating dynamic predictions about beta-diversity in ecological communities. Ecologists can achieve an understanding of the assembly rules operating in nature by noting when and how these predictions are met or not met. This is particularly valuable for those groups of organisms that are challenging to study under natural conditions (e.g., bacteria and fungi). Here, we focused on arbuscular mycorrhizal fungal (AMF) communities and performed an extensive literature search that allowed us to synthesize the information in 19 data sets with the minimal requisites for creating a null hypothesis in terms of community dissimilarity expected under neutral dynamics. In order to achieve this task, we calculated the first estimates of neutral parameters for several AMF communities from different ecosystems. Communities were shown either to be consistent with neutrality or to diverge or converge with respect to the levels of compositional dissimilarity expected under neutrality. These data support the hypothesis that divergence occurs in systems where the effect of limited dispersal is overwhelmed by anthropogenic disturbance or extreme biological and environmental heterogeneity, whereas communities converge when systems have the potential for niche divergence within a relatively homogeneous set of environmental conditions. Regarding the study cases that were consistent with neutrality, the sampling designs employed may have covered relatively homogeneous environments in which the effects of dispersal limitation overwhelmed minor differences among AMF taxa that would lead to environmental filtering. Using neutral models we showed for the first time for a soil microbial group the conditions under which different assembly processes may determine different patterns of beta-diversity. Our synthesis is an important step showing how the application of general ecological theories to a model microbial taxon has the potential to shed light on the assembly and ecological dynamics of communities.

IgA antibody production by intrarectal immunization of mice using recombinant major capsid protein of hamster polyomavirus.

Viral proteins are highly antigenic and known as potent stimulators of adaptive immune responses. This mechanism is often used for biotechnological applications in monoclonal antibody production resulting in high-affinity IgG antibodies in most cases. The aim of this study was to increase antigen-specific IgA antibody levels in mice in order to generate monoclonal IgA antibodies by hybridoma technology. For this purpose, hamster polyomavirus (HaPyV) major capsid protein VP1 was used to immunize mice by different routes in order to induce VP1-specific IgA titers. Recombinant HaPyV-VP1 was generated in Escherichia coli and administered intraperitoneally, orally, and intrarectally. VP1-specific antibodies were determined by ELISA in sera and organ culture supernatants. We found a significant increase of HaPyV-VP1-specific IgAs in spleen organ cultures after rectal immunization of mice but not in cultures of mesenteric lymph nodes, colon, or Peyer's patches. In contrast, oral and intraperitoneal immunization did not provide an appropriate specific IgA induction at all. These results show that specific IgA antibodies can be induced by intrarectal immunization in the spleen. The generation of monoclonal IgA antibodies with well-defined properties is a useful tool for the investigation of mucosal immune responses or autoimmune diseases and extends the spectrum of antibodies with specific effector functions.

Inner composition alignment for inferring directed networks from short time series.

Identifying causal links (couplings) is a fundamental problem that facilitates the understanding of emerging structures in complex networks. We propose and analyze inner composition alignment-a novel, permutation-based asymmetric association measure to detect regulatory links from very short time series, currently applied to gene expression. The measure can be used to infer the direction of couplings, detect indirect (superfluous) links, and account for autoregulation. Applications to the gene regulatory network of E. coli are presented.

Identifying quality improvement intervention evaluations: is consensus achievable?

BACKGROUND: The diversity of quality improvement interventions (QIIs) has impeded the use of evidence review to advance quality improvement activities. An agreed-upon framework for identifying QII articles would facilitate evidence review and consensus around best practices. AIM: To adapt and test evidence review methods for identifying empirical QII evaluations that would be suitable for assessing QII effectiveness, impact or success. DESIGN: Literature search with measurement of multilevel inter-rater agreement and review of disagreement. METHODS: Ten journals (2005-2007) were searched electronically and the output was screened based on title and abstract. Three pairs of reviewers then independently rated 22 articles, randomly selected from the screened list. Kappa statistics and percentage agreement were assessed. 12 stakeholders in quality improvement, including QII experts and journal editors, rated and discussed publications about which reviewers disagreed. RESULTS: The level of agreement among reviewers for identifying empirical evaluations of QII development, implementation or results was 73% (with a paradoxically low kappa of 0.041). Discussion by raters and stakeholders regarding how to improve agreement focused on three controversial article selection issues: no data on patient health, provider behaviour or process of care outcomes; no evidence for adaptation of an intervention to a local context; and a design using only observational methods, as correlational analyses, with no comparison group. CONCLUSION: The level of reviewer agreement was only moderate. Reliable identification of relevant articles is an initial step in assessing published evidence. Advancement in quality improvement will depend on the theory- and consensus-based development and testing of a generalizable framework for identifying QII evaluations.

Finding order in heterogeneity: types of quality-improvement intervention publications.

BACKGROUND: Stakeholders in quality improvement agree on the need for augmenting and synthesising the scientific literature supporting it. The diversity of perspectives, approaches, and contexts critical to advancing quality improvement science, however, creates challenges. The paper explores the heterogeneity in clinical quality improvement intervention (QII) publications. METHODS: A preliminary classification framework was developed for QII articles, aiming for categories homogeneous enough to support coherent scientific discussion on QII reporting standards and facilitate systematic review. QII experts were asked to identify articles important to QII science. The framework was tested and revised by applying it to the article set. The final framework screened articles into (1) empirical literature on development and testing of QIIs; (2) QII stories, theories, and frameworks; (3) QII literature syntheses and meta-analyses; or (4) development and testing of QII-related tools. To achieve homogeneity, category (1) required division into (1a) development of QIIs; 1(b) history, documentation, or description of QIIs; or (1c) success, effectiveness or impact of QIIs. RESULTS: By discussing unique issues and established standards relevant to each category, QII stakeholders can advance QII practice and science, including the scope and conduct of systematic literature reviews.

Community structure of arbuscular mycorrhizal fungi associated to Veronica rechingeri at the Anguran zinc and lead mining region.

Root colonization and diversity of arbuscular mycorrhizal fungi (AMF) were analyzed in Veronica rechingeri growing in heavy metal (HM) and non-polluted soils of the Anguran Zn and Pb mining region (Iran). Three species could be separated morphologically, while phylogenetic analyses after PCR amplification of the ITS region followed by RFLP and sequencing revealed seven different AMF sequence types all within the genus Glomus. Rarefaction analysis confirmed exhaustive molecular characterization of the AMF diversity present within root samples. Increasing heavy metal contamination between the sites studied was accompanied by a decrease in AMF spore numbers, mycorrhizal colonization parameters and the number of AMF sequence types colonizing the roots. Some AMF sequence types were only found at sites with the highest and lowest soil HM contents, respectively.

Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies.

BACKGROUND: The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners. METHOD: A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively. RESULTS: Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice. CONCLUSIONS: Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.

Hepatocyte proliferation and apoptosis in rat liver after liver injury.

BACKGROUND/AIMS: In this paper the early phase of proliferate response and apoptosis of hepatocytes after partial liver resection, during reperfusion after ischemia and during sepsis is demonstrated. METHODOLOGY: Experiments were conducted in a rat model with regeneration times of 0.5-24 hours after injury. Proliferation was analyzed by Ki-67 immunohistochemistry and confirmed by double staining with CK18 in FACS. Apoptosis was analyzed by TUNEL technique. RESULTS: Periportal hepatocytes enter the cell cycle already 0.5-2 hours after injury in all three models. This early proliferative response is predominant periportally localized. During reperfusion and during sepsis there was a strict pericentral apoptosis of hepatocytes found. CONCLUSIONS: An early periportal proliferation of hepatocytes is a common reaction of the liver to injury. This proliferation takes place much earlier then the main proliferative response 24-72 h after partial resection. This predominant periportal proliferation together with the pericentral apoptosis fit to the concept of the "streaming liver" in liver regeneration.

Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors.

AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liver regeneration 24 h after the damage might be not successful.

Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation.

OBJECTIVES: To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults. DATA SOURCES: Electronic databases from inception to October 2003, updated in August 2004. REVIEW METHODS: A systematic review was undertaken according to published guidelines. Decision analytic modelling was undertaken, based on the findings of the review, expert opinion and additional information from the literature, to assess the relative cost-effectiveness of plausible alternative tests that are part of diagnostic algorithms for haematuria. RESULTS: A total of 118 studies met the inclusion criteria. No studies that evaluated the effectiveness of diagnostic algorithms for haematuria or the effectiveness of screening for haematuria or investigating its underlying cause were identified. Eighteen out of 19 identified studies evaluated dipstick tests and data from these suggested that these are moderately useful in establishing the presence of, but cannot be used to rule out, haematuria. Six studies using haematuria as a test for the presence of a disease indicated that the detection of microhaematuria cannot alone be considered a useful test either to rule in or rule out the presence of a significant underlying pathology (urinary calculi or bladder cancer). Forty-eight of 80 studies addressed methods to localise the source of bleeding (renal or lower urinary tract). The methods and thresholds described in these studies varied greatly, precluding any estimate of a 'best performance' threshold that could be applied across patient groups. However, studies of red blood cell morphology that used a cut-off value of 80% dysmorphic cells for glomerular disease reported consistently high specificities (potentially useful in ruling in a renal cause for haematuria). The reported sensitivities were generally low. Twenty-eight studies included data on the accuracy of laboratory tests (tumour markers, cytology) for the diagnosis of bladder cancer. The majority of tumour marker studies evaluated nuclear matrix protein 22 or bladder tumour antigen. The sensitivity and specificity ranges suggested that neither of these would be useful either for diagnosing bladder cancer or for ruling out patients for further investigation (cystoscopy). However, the evidence remains sparse and the diagnostic accuracy estimates varied widely between studies. Fifteen studies evaluating urine cytology as a test for urinary tract malignancies were heterogeneous and poorly reported. The calculated specificity values were generally high, suggesting some possible utility in confirming malignancy. However, the evidence suggests that urine cytology has no application in ruling out malignancy or excluding patients from further investigation. Fifteen studies evaluated imaging techniques [computed tomography (CT), intravenous urography (IVU) or ultrasound scanning (US)] to detect the underlying cause of haematuria. The target condition and the reference standard varied greatly between these studies. The diagnostic accuracy data for several individual studies appeared promising but meaningful comparison of the available imaging technologies was impossible. Eight studies met the inclusion criteria but addressed different parts of the diagnostic chain (e.g. screening programmes, laboratory investigations, full urological work-up). No single study addressed the complete diagnostic process. The review also highlighted a number of methodological limitations of these studies, including their lack of generalisability to the UK context. Separate decision analytic models were therefore developed to progress estimation of the optimal strategy for the diagnostic management of haematuria. The economic model for the detection of microhaematuria found that immediate microscopy following a positive dipstick test would improve diagnostic efficiency as it eliminates the high number of false positives produced by dipstick testing. Strategies that use routine microscopy may be associated with high numbers of false results, but evidence was lacking regarding the accuracy of routine microscopy and estimates were adopted for the model. The model for imaging the upper urinary tract showed that US detects more tumours than IVU at one-third of the cost, and is also associated with fewer false results. For any cause of haematuria, CT was shown to have a mean incremental cost-effectiveness ratio of pounds sterling 9939 in comparison with the next best option, US. When US is followed up with CT for negative results with persistent haematuria, it dominates the initial use of CT alone, with a saving of pounds sterling 235,000 for the evaluation of 1000 patients. The model for investigation of the lower urinary tract showed that for low-risk patients the use of immediate cystoscopy could be avoided if cystoscopy were used for follow-up patients with a negative initial test using tumour markers and/or cytology, resulting in a saving of pounds sterling 483,000 for the evaluation of 1000 patients. The clinical and economic impact on delayed detection of both upper and lower urinary tract tumours through the use of follow-up testing should be evaluated in future studies. CONCLUSIONS: There are insufficient data currently available to derive an evidence-based algorithm of the diagnostic pathway for haematuria. A hypothetical algorithm based on the opinion and practice of clinical experts in the review team, other published algorithms and the results of economic modelling is presented in this report. This algorithm is presented, for comparative purposes, alongside current US and UK guidelines. The ideas contained in these algorithms and the specific questions outlined should form the basis of future research. Quality assessment of the diagnostic accuracy studies included in this review highlighted several areas of deficiency.

Zonation of hepatic bile salt transporters.

Pericentral and periportal hepatocytes differ in their capacity to eliminate and velocity of eliminating bile acids and other organic anions. We wonder whether differences in the distribution of anion transporters (ntcp [M77479], besp [NM_031760], mrp2 [NM_012833], oatp1 [NM_017111], oatp2 [NM_131906]) cause the differences in bile acid excretion. Therefore, we analyzed the distribution of these anion transporters in periportal and pericentral cells by immunohistology, their mRNA by quantitative PCR, and regulating nuclear factors (NF-kappaB, HNF1, HNF3, HNF4, FXR, PXR) by gel shift assay. We did not find any differences in nuclear factors or regarding the proteins that could explain the zonal differences in anion transport.