Nocturnal Hypoxia and Loss of Kidney Function

Background: Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods: We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90 % for $12$4 ml/min/1.73 m2 per year. Results: 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95 % confidence interval [CI] 1.25, 6.67). Conclusion: Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up.The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used.31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors.In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis

An Application of the Concept of the Therapeutic Alliance To Sadomasochistic Pathology

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66889/2/10.1177_00030651980460031301.pd

Peritoneal changes due to laparoscopic surgery

Item does not contain fulltextBACKGROUND: Laparoscopic surgery has been incorporated into common surgical practice. The peritoneum is an organ with various biologic functions that may be affected in different ways by laparoscopic and open techniques. Clinically, these alterations may be important in issues such as peritoneal metastasis and adhesion formation. METHODS: A literature search using the Pubmed and Cochrane databases identified articles focusing on the key issues of laparoscopy, peritoneum, inflammation, morphology, immunology, and fibrinolysis. Results : Laparoscopic surgery induces alterations in the peritoneal integrity and causes local acidosis, probably due to peritoneal hypoxia. The local immune system and inflammation are modulated by a pneumoperitoneum. Additionally, the peritoneal plasmin system is inhibited, leading to peritoneal hypofibrinolysis. CONCLUSION: Similar to open surgery, laparoscopic surgery affects both the integrity and biology of the peritoneum. These observations may have implications for various clinical conditions.1 januari 201

Spatiotemporal modeling of microbial metabolism

Background Microbial systems in which the extracellular environment varies both spatially and temporally are very common in nature and in engineering applications. While the use of genome-scale metabolic reconstructions for steady-state flux balance analysis (FBA) and extensions for dynamic FBA are common, the development of spatiotemporal metabolic models has received little attention. Results We present a general methodology for spatiotemporal metabolic modeling based on combining genome-scale reconstructions with fundamental transport equations that govern the relevant convective and/or diffusional processes in time and spatially varying environments. Our solution procedure involves spatial discretization of the partial differential equation model followed by numerical integration of the resulting system of ordinary differential equations with embedded linear programs using DFBAlab, a MATLAB code that performs reliable and efficient dynamic FBA simulations. We demonstrate our methodology by solving spatiotemporal metabolic models for two systems of considerable practical interest: (1) a bubble column reactor with the syngas fermenting bacterium Clostridium ljungdahlii; and (2) a chronic wound biofilm with the human pathogen Pseudomonas aeruginosa. Despite the complexity of the discretized models which consist of 900 ODEs/600 LPs and 250 ODEs/250 LPs, respectively, we show that the proposed computational framework allows efficient and robust model solution. Conclusions Our study establishes a new paradigm for formulating and solving genome-scale metabolic models with both time and spatial variations and has wide applicability to natural and engineered microbial systems

Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. METHODS: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. RESULTS: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. CONCLUSIONS: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.LUPUS UK Rosetrees Trust Arthritis Research UK Programme Grant National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre Canadian Institutes of Health Research Hanyang University Sandwell and West Birmingham Hospitals National Health Service (NHS) Trust IHR/Wellcome Trust Clinical Research Facility in Birmingham National Institutes of Health (NIH) Singer Family Fund for Lupus Research Arthritis Research UK National Institute for Health Research Manchester Biomedical Research Unit NIHR/Wellcome Trust Manchester Clinical Research Facility Danish Rheumatism Association Novo Nordisk Foundation NIH Department of Education, Universities and Research of the Basque Government Arthritis Research U

Integrating Flux Balance Analysis into Kinetic Models to Decipher the Dynamic Metabolism of Shewanella oneidensis MR-1

Shewanella oneidensis MR-1 sequentially utilizes lactate and its waste products (pyruvate and acetate) during batch culture. To decipher MR-1 metabolism, we integrated genome-scale flux balance analysis (FBA) into a multiple-substrate Monod model to perform the dynamic flux balance analysis (dFBA). The dFBA employed a static optimization approach (SOA) by dividing the batch time into small intervals (i.e., ∼400 mini-FBAs), then the Monod model provided time-dependent inflow/outflow fluxes to constrain the mini-FBAs to profile the pseudo-steady-state fluxes in each time interval. The mini-FBAs used a dual-objective function (a weighted combination of “maximizing growth rate” and “minimizing overall flux”) to capture trade-offs between optimal growth and minimal enzyme usage. By fitting the experimental data, a bi-level optimization of dFBA revealed that the optimal weight in the dual-objective function was time-dependent: the objective function was constant in the early growth stage, while the functional weight of minimal enzyme usage increased significantly when lactate became scarce. The dFBA profiled biologically meaningful dynamic MR-1 metabolisms: 1. the oxidative TCA cycle fluxes increased initially and then decreased in the late growth stage; 2. fluxes in the pentose phosphate pathway and gluconeogenesis were stable in the exponential growth period; and 3. the glyoxylate shunt was up-regulated when acetate became the main carbon source for MR-1 growth

Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach.

OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE

Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus

Background: Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. Methods: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. Results: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). Conclusion: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis

Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE.Recently diagnosed (1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort.MetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course.Canadian Institutes of Health Research 93695 86526 Arthritis Research UK (Arthritis Research UK Epidemiology Unit Core Support Programme Grant) National Institute for Health Research (NIHR) Biomedical Research Unit Funding Scheme NIHR Manchester Biomedical Research Centre Arthritis Research UK Manchester Academic Health Science Centre NIHR Biomedical Research Unit Funding Scheme NIHR Manchester Wellcome Trust Clinical Research Facility Arthritis Research Clinical Research Fellowship 18845 Ministry for Health and Welfare, Republic of Korea A120404 Lupus UK NIHR/Wellcome Trust Clinical Research Facility at University Hospital Birmingham NHS Foundation Trust and City Hospital Sandwell and West Birmingham Hospitals NHS Trust, UK NIH UL1 RR025741 P60AR 30692 K24 AR 002138 RR00046 Hopkins Lupus Cohort NIH RD-1 43727 Department of Education, Universities and Research, Basque Government Singer Family Fund for Lupus Research tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases, Universite Lava