A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients

Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter

In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter.The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports.The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice.All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines.Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.Overall, higher troughs ( >15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of >15 mg/liter.The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37).The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event.An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration.Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy

Gastrointestinal pathogen distribution in symptomatic children in Sydney, Australia

There is limited information on the causes of paediatric diarrhoea in Sydney. This cross-sectional study used clinical and microbiological data to describe the clinical features and pathogens associated with gastrointestinal illnesses for children presenting to two major public hospitals in Sydney with diarrhoea, for the period January 2007-December 2010.Of 825 children who tested positive for an enteric pathogen, 430 medical records were reviewed. Adenovirus, norovirus and rotavirus were identified in 20.8%, 20.3% and 21.6% of reviewed cases, respectively. Younger children were more likely to have adenovirus and norovirus compared with rotavirus (P=0.001). More viruses were detected in winter than in the other three seasons (P=0.001). Rotavirus presented a distinct seasonal pattern with the lowest rates occurring in the warm months and peaking in the cooler months. Adenovirus showed a less consistent monthly trend, and norovirus detection increased in the cooler months (P=0.008). A decline in the number of rotavirus cases was observed after mid-2008.The majority of childhood diarrhoeal illnesses leading to hospital presentations in Sydney are caused by enteric viruses with most infections following clear seasonal patterns. However, a sustained decrease in the incidence of rotavirus infections has been observed over the study period. © 2012 Ministry of Health, Saudi Arabia

Epidemiology and geographical distribution of enteric protozoan infections in Sydney, Australia

© 2014 S. Fletcher et al., 2014. Results: Frequently detected protozoa were Blastocystis spp. (57%), Giardia intestinalis (27%) and Dientamoeba fragilis (12%). The age distribution showed that the prevalence of protozoa decreased with age up to 24 years but increasing with age from 25 years onwards. The geographic provenance of the patients indicates that the majority of cases of Blastocystis (53.1%) are clustered in and around the Sydney City Business District, while pockets of giardiasis were identified in regional/rural areas. The distribution of cases suggests higher risk of protozoan infection may exist for some communities.Conclusions: These findings provide useful information for policy makers to design and tailor interventions to target high risk communities Follow-up investigation into the risk factors for giardiasis in regional/rural areas is needed.Background: Enteric protozoa are associated with diarrhoeal illnesses in humans; however there are no recent studies on their epidemiology and geographical distribution in Australia. This study describes the epidemiology of enteric protozoa in the state of New South Wales and incorporates spatial analysis to describe their distribution.Design and methods: Laboratory and clinical records from four public hospitals in Sydney for 910 patients, who tested positive for enteric protozoa over the period January 2007 - December 2010, were identified, examined and analysed. We selected 580 cases which had residence post code data available, enabling us to examine the geographic distribution of patients, and reviewed the clinical data of 252 patients to examine possible links between protozoa, demographic and clinical features

Underwater acoustic characteristics of the OWEZ wind farm operation (T1)

In Holland the first two offshore wind farms, the Offshore Wind Farm Egmond aan Zee (OWEZ) and “Prinses Amalia” were built in respectively 2006 and 2007. Beside the main goal of producing electric energy from wind resource the construction of the first wind farm (OWEZ) was also used to demonstrate the impact of such construction to the environment. To demonstrate the impact an extensive Monitoring and Evaluation Program (MEP) was developed to evaluate the effects on benthic organisms, fish, birds and marine mammals. One of the tasks was to measure the underwater noise characteristics before and during the construction and with turbines in operation and to estimate the effects

Reply to "vancomycin-induced nephrotoxicity"

[No abstract available

Au-Ag template stripped pattern for scanning probe investigations of DNA arrays produced by Dip Pen Nanolithography

We report on DNA arrays produced by Dip Pen Nanolithography (DPN) on a novel Au-Ag micro patterned template stripped surface. DNA arrays have been investigated by atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) showing that the patterned template stripped substrate enables easy retrieval of the DPN-functionalized zone with a standard optical microscope permitting a multi-instrument and multi-technique local detection and analysis. Moreover the smooth surface of the Au squares (abput 5-10 angstrom roughness) allows to be sensitive to the hybridization of the oligonucleotide array with label-free target DNA. Our Au-Ag substrates, combining the retrieving capabilities of the patterned surface with the smoothness of the template stripped technique, are candidates for the investigation of DPN nanostructures and for the development of label free detection methods for DNA nanoarrays based on the use of scanning probes.Comment: Langmuir (accepted

Mode of onset of torsade de pointes in congenital long QT syndrome

Objectives.We sought to describe the mode of onset of spontaneous torsade de pointes in the congenital long QT syndrome.Background.Contemporary classifications of the long QT syndrome (LQTS) refer to the congenital LQTS as “adrenergic dependent” and to the acquired LQTS as “pause dependent.” Overlap between these two categories has been recognized, and a subgroup of patients with “idiopathic pause-dependent torsade” has been described. However, it is not known how commonly torsade is preceded by pauses in the congenital LQTS.Methods.We reviewed the electrocardiograms (ECGs) of all our patients with congenital LQTS evaluated for syncope or sudden death (30 patients). Documentation of the onset of torsade de pointes was available for 15 patients. All these patients had “definitive LQTS” by accepted clinical and ECG criteria.Results.Pause-dependent torsade de pointes was clearly documented in 14 of the 15 patients (95% confidence interval 68% to 100%). The cycle length of the pause leading to torsade was 1.3 ± 0.2 times longer than the basic cycle length, and most pauses leading to torsade were unequivocally longer than the preceding basic cycle length (80% of pauses were >80 ms longer than the preceding cycle length).Conclusions.The “long-short” sequence, which has been recognized as a hallmark of torsade de pointes in the acquired LQTS, plays a major role in the genesis of torsade in the congenital LQTS as well. Our findings have important therapeutic implications regarding the use of pacemakers for prevention of torsade in the congenital LQTS