Presentation and clinical course of pediatric-onset versus adult-onset Takayasu arteritis—a systematic review and meta-analysis

Clinical Rheumatology - Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and adult-onset...     

Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system

Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99‐100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long‐distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99‐100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015. All patients had at least 6 months post‐transplant follow‐up. The mean follow‐up was 13.9±3 months in cPRA ≥99% and 12.3±3.5 months in cPRA ≤98%. There was a total of 152 transplants, 25 study patients, and 127 controls. No statistically significant differences were found between the two groups in delayed graft function, rejection, kidney function, graft and patient survival, or infections. We conclude that transplanting the most highly sensitized patients with kidneys shared outside their local donation service areas is associated with excellent short‐term outcomes that are comparable to controls.     

Blood donation, body iron status and carotid intima-media thickness

Iron could promote free radical formation, which may lead to injury of the arterial wall and atherosclerosis. Blood donation may reduce cardiovascular risk by lowering body iron status. We collected data on blood donation history and intima-media thickness of the common carotid artery (CIMT) in 819 subjects (50-70 years), who were recruited from municipal and blood bank registries in The Netherlands. Serum iron parameters were assessed, including non-transferrin bound iron (NTBI) that has recently been found in conditions of iron overload. Serum ferritin was lower in current donors (n=443; 44 microg/L) than in ex-donors (n=120; 114 microg/L) and never-donors (n=256; 124 microg/L, P for trend <0.001). For NTBI, values were 2.33, 2.54, and 2.51 micromol/L, respectively (P<0.05). CIMT was slightly reduced in frequent donors (i.e., > or =49 times during life or > or =2 times per year), although not statistically significant. CIMT was not significantly related to NTBI. Frequent blood donation, resulting in lowered body iron, might give some protection against accelerated atherosclerosis.     

An ultrasensitive label free nanobiosensor platform for the detection of cardiac biomarkers

We report the fabrication of a label free nano biosensor platform comprising single nanofiber that is derived out of multi-walled carbon nanotubes (MWCNTs) embedded SU-8 photoresist, for the detection of three important human cardiac biomarkers viz., myoglobin (Myo), cardiac Troponin I (cTn I) and Creatine Kinase-MB (CK-MB). These composite nanofibers were synthesized using electrospinning process. Single nanofibers were aligned between pairs of electrodes in-situ during the electrospinning process. The target proteins were detected using chemiresistive detection methodology. Each biomarker was detected using a specific, single, aligned nanofiber, functionalized with its corresponding monoclonal antibody. Chemiresistive detection involves measuring the change in conductance of the functionalized nanofibers upon the binding of the targeted antigen. The minimum detection limits of Myo, CK-MB and cTn I were experimentally found out to be as low as 6, 20 and 50 fg/ml respectively. No response was observed when the nanofibers were exposed to a non-specific protein, demonstrating excellent specificity to the targeted detection. These MWCNTs embedded SU-8 nanofibers based nanobiosensor platform shows great promise in the detection of cardiac markers and other proteins as they have fast response time, high sensitivity and good specificity.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Sleep disorders: Serious threats among kidney transplant recipients

In patients with chronic kidney disease (CKD) and kidney transplant recipients who continue to have some degree of CKD, the prevalence of sleep-related disorders is very high. Common sleep disorders in both groups include insomnia, sleep-disordered breathing (SDB), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), and others. Depending on the kidney graft function, some patients see sleep disorders resolve after kidney transplantation, while others continue to have persistent sleep disorders or develop new ones. Kidney transplant recipients (KTRs) are unique patients due to the presence of a single kidney, the use of immunosuppressive medications, and other comorbidities including obesity, a high risk of cardiovascular disease, malignancy, and the anxiety of losing their allograft. All of these factors contribute to the risk for sleep disorders. CKD and sleep disorders have a bidirectional relationship; that is, CKD may increase the risk of sleep disorders and sleep disorders may increase the risk of CKD. Obstructive sleep apnea (OSA) is the most common form of SDB and is known to alter renal hemodynamics. OSA leads to hypoxemia and sleeps fragmentation, which activates the sympathetic nervous system. This activates the renin-angiotensin-aldosterone system and ultimately alters cardiovascular hemodynamics. Sleep disorders may have deleterious effects on the kidney allograft and proper screening and management are important for both graft and patient survival.     

Rapid simultaneous determination of telmisartan, amlodipine besylate and hydrochlorothiazide in a combined poly pill dosage form by stability-indicating ultra performance liquid chromatography

A simple, precise and rapid stability-indicating ultra-performance liquid chromatography (UPLC) method is developed for the simultaneous quantitative determination of Telmisartan, Amlodipine besylate and Hydrochlorothiazide from their innovative poly pill combination drug product in the presence of degradation products. It involves a 100 mm x 2.1 mm, 1.7 μm C-18 column. The separation is achieved on a simple gradient method. The mobile phase A contains a mixture of sodium perchlorate buffer pH 3.2 (0.053M): acetonitrile in the ratio 90:10, v/v, and mobile B contains a mixture of sodium perchlorate buffer pH 3.2 (0.053M): acetonitrile in the ratio 20:80, v/v. The flow rate is 0.6 mL min(-1) and the column temperature is maintained at 55°C.The gradient program (T/%B) is set as 0/5, 1.2/5, 1.6/40, 4/40, 4.1/5 and 4.5/5. The detector wavelength is 271 nm for Hydrochlorothiazide and Telmisartan and 237 nm for Amlodipine. The retention times of Telmisartan, Amlodipine, and Hydrochlorothiazide are 3.6 minutes, 3.2 minutes and 0.9 minutes; respectively. The total runtime for the separation of the three active compounds and their degradation products is 4.5 minutes. The described method is validated with respect to system suitability, specificity, linearity, precision and accuracy. The precision of the assay method is evaluated by carrying out six independent assays of T, A and H (0.032 mg mL(-1) of T, 0.004 mg mL(-1) of A, 0.01 mg mL(-1) of H). The accuracy of the method is evaluated in triplicate at three concentration levels, i.e. 50%, 100% and 150% of target test concentration (0.64 mg mL(-1) of T, 0.08 mg mL(-1) of A, 0.2 mg mL(-1) of H). The described method is linear over the range, 16 to 48 μg mL(-1) for T, 2 to 6 μg mL(-1)A and 5 to 15 μg mL(-1) for H. The method is fast and suitable for high-throughput analysis allowing the analysis of about 250 samples per working day.     

Subcellular distribution of α1G subunit of T‐type calcium channel in the mouse dorsal lateral geniculate nucleus

T‐type calcium channels play a pivotal role in regulating neural membrane excitability in the nervous system. However, the precise subcellular distributions of T‐type channel subunits and their implication for membrane excitability are not well understood. Here we investigated the subcellular distribution of the α1G subunit of the calcium channel which is expressed highly in the mouse dorsal lateral geniculate nucleus (dLGN). Light microscopic analysis demonstrated that dLGN exhibits intense immunoperoxidase reactivity for the α1G subunit. Electron microscopic observation showed that the labeling was present in both the relay cells and interneurons and was found in the somatodendritic, but not axonal, domains of these cells. Most of the immunogold particles for the α1G subunit were either associated with the plasma membrane or the intracellular membranes. Reconstruction analysis of serial electron microscopic images revealed that the intensity of the intracellular labeling exhibited a gradient such that the labeling density was higher in the proximal dendrite and progressively decreased towards the distal dendrite. In contrast, the plasma membrane‐associated particles were distributed with a uniform density over the somatodendritic surface of dLGN cells. The labeling density in the relay cell plasma membrane was about 3‐fold higher than that of the interneurons. These results provide ultrastructural evidence for cell‐type‐specific expression levels and for uniform expression density of the α1G subunit over the plasma membrane of dLGN cells. J. Comp. Neurol. 518:4362–4374, 2010. © 2010 Wiley‐Liss, Inc.     

Gender and body size affect the response of erythrocyte folate to folic acid treatment

The recommended dietary allowance (RDA) differs between men and women for some vitamins, but not for folate. The RDA for folate is derived mainly from metabolic studies in women. We assessed if men differ from women in their response of erythrocyte folate to folic acid supplementation. We used data from 2 randomized placebo-controlled trials with folic acid: a 3-y trial in which subjects ingested 800 mug/d of folic acid (294 men and 112 women) and a 12-wk trial in which 187 men and 129 women ingested 0, 50, 100, 200, 400, 600, or 800 microg/d of folic acid in a parallel design (n = 38-42 per treatment group). In the 3-y trial, the erythrocyte folate concentration increased 10% (143 nmol/L, [95%CI 46, 241]) less in men than in women. In the 12-wk trial, regression analysis showed that the response of erythrocyte folate upon folic acid intake for men was 47 nmol/L lower than for women (P for beta(gender) = 0.022); for an intake of 800 microg/d folic acid, this resulted in a 5% lower response in men than in women. Differences in lean body size explained 56% of the difference in response of erythrocyte folate between men and women in the 3-y trial and 70% in the 12-wk trial. Men need more folic acid than women to achieve the same erythrocyte folate concentration, mainly because men have a larger lean body mass. This could be an indication that the RDA for folate should be higher for men than for women, or that the RDA should be expressed per kilogram of lean body mass.