Renal artery stenting for renal artery stenosis: interventional approach and initial clinical results

BACKGROUND: Significant renal artery stenosis is being increasingly diagnosed and interventional cardiologists are taking on the unfamiliar role of deploying renal stents. We describe our technique for renal artery stenting using techniques and equipment similar to that used in coronary stenting and present early results. METHODS: Thirty-two patients with significant renal artery stenosis (diameter stenosis 60-95%) and difficult to control hypertension or renal impairment were referred for renal stenting. Renal DTPA scans were performed before intervention. All the procedures were attempted from the femoral artery approach using guides, low profile wires and balloon catheters similar to those used for coronary work. The lowest profile renal or coronary stents were deployed using a monorail technique. RESULTS: Atherosclerosis was the cause of the renal artery stenosis in 31 patients. Stents were successfully deployed in 30 of these patients (97%). One patient required a second procedure from the brachial artery approach. An additional patient with fibromuscular dysplasia underwent angioplasty only. Angiographic diameter stenosis was reduced from a mean of 79 to 1%. Translesional mean pressure gradients were reduced from 22 to 1mmHg. There were no major procedural or in-hospital complications. Anti-hypertensive drugs were reduced from a mean of 3 prior to stenting to 0.7 at discharge. Renal DTPA scans were a poor predictor of severity of stenosis. Renal DTPA scans suggested functionally significant renal artery stenosis in only 48% of patients but the clinical responses suggested that this was an underestimate. CONCLUSIONS: Stenting of renal arteries using coronary like techniques and equipment results in a high rate of procedural success and good early clinical outcomes.     

Functional and morphological changes in the microcirculation of the dog following acute coronary artery ligation

Acute ligation of the anterior descending coronary artery in the dog had little immediate effect on heat clearance but immediately lowered heat production, which fell to its minimum level in 1/2 hr, after which it began to recover; recovery was complete in 6 hr. After 1/2 hr heat clearance also began to fall and reached a minimum level in 1 1/2 hr. Ligation increased oxygen extraction but reduced oxygen consumption markedly though temporarily. Complete recovery followed. After 3 months, there was full recovery in flow, oxygen extraction ratio, and oxygen consumption mVO2. In morphological studies using Microfil injections soon after ligation, capillaries failed to fill retrogradely, though network vessels were perfused. After 1 hr of acute artery ligation, capillaries still did not perfuse but by 3 hr there was some reperfusion. After 6 hr there was marked capillary reperfusion. In dogs kept for 3 months after ligation the microcirculation was normal. These studies confirm that immediate circulatory failure occurred in capillaries (probably critical closure) which accounts for the immediate fall in venous outflow, heat production, and mVO2. Flow continued in network vessels which traversed the ischemic zone without perfusing capillaries. These results are contrasted with the findings of some other workers who found a continued functional decline leading to infarction. The present results were accounted for by closure and reopening to capillaries.     

Controlled proteolysis of the multifunctional protein that initiates pyrimidine biosynthesis in mammalian cells: evidence for discrete structural domains.

The multifunctional protein that initiates de novo pyrimidine biosynthesis in mammalian cells carries carbamoylphosphate synthetase, aspartate transcarbamylase (aspartate carbamoyltransferase), and dihydro-orotase activities on a single 215,000-dalton polypeptide chain. Kinetic studies of the controlled proteolysis of the molecule by elastase showed that the protein was not attacked at random by the protease but rather was successively cleaved into at least six well-defined proteolytic fragments. The initial cleavage converted the intact molecule into a 190,000-dalton species which appeared to retain all of the catalytic and regulatory functions of the native protein. This species was subsequently cleaved into two fragments, 150,000 and 40,000 daltons. The 40,000-dalton species, which carried the aspartate transcarbamylase activity, was resistant to further proteolysis; the 150,000-dalton polypeptide, which carried carbamoyl-phosphate synthetase and dihydro-orotase activities, underwent further digestion to 140,000 daltons. Continued proteolysis produced two species, 79,000 and 45,000 daltons; like the 40,000-dalton species, these were stable against further elastase digestion. The aspartate transcarbamylase and dihydro-orotase activities and the regulatory functions were preserved throughout the course of digestion; the carbamoylphosphate synthetase activity was more labile. By using sucrose gradient centrifugation and ion exchange chromatography, the 40,000- and 45,000-dalton species have been isolated. The 40,000-dalton fragment was found to have only aspartate transcarbamylase activity; the 45,000-dalton fragment has only dihydro-orotase activity. These experiments showed that this multifunctional protein is organized as discrete structural domains in which regions of the polypeptide chain are autonomously folded into separate functional units.     

A systematic review comparing clinical features in early age at onset and late age at onset late-life depression

Background

Although evidence suggests that there are neurobiological differences between unipolar depression in younger versus older adults, conflicting evidence exists about whether these manifest as clinically identifiable differences.

Method

We conducted a systematic review of aetiological, phenomenological and outcome studies to examine the evidence for a distinction between early onset (EOD) and late onset (LOD) depression. A literature search was completed using the computer databases MEDLINE, EMBASE, PSYCHINFO and PUBMED for papers published between January 1982 and December 2012 which compared groups with EOD and LOD. Studies were included if they were of older people and compared symptoms, aetiological factors or outcomes. We conducted a quality assessment of included articles.

Results

We identified 23 articles which met entry criteria. The only clinical feature which was different between the groups was a higher frequency of a family history of mood disorders in EOD.

Limitations

The number of studies identified was low and their quality was generally poor.

Conclusions

Although neurobiological studies have reported differences between EOD and LOD, generally these do not appear to translate into identifiable distinguishing clinical features.     

TREX1 D18N mice fail to process erythroblast DNA resulting in inflammation and dysfunctional erythropoiesis

Abstract

Anaemia is commonly observed in chronic inflammatory conditions, including systemic lupus erythematosus (SLE), where ～50% of patients display clinical signs of anaemia. Mutation at the aspartate residue 18 of the three prime repair exonuclease 1 (TREX1) gene causes a monogenic form of cutaneous lupus in humans and the genetically precise TREX1 D18N mice recapitulate a lupus-like disease. TREX1 degrades single- and double-stranded DNA (dsDNA), and the link between failed DNA degradation by nucleases, including nucleoside-diphosphate kinases (NM23H1/H2) and Deoxyribonuclease II (DNase II), and anaemia prompted our studies to investigate whether TREX1 dysfunction contributes to anaemia. Utilizing the TREX1 D18N mice we demonstrate that (1) TREX1 mutant mice develop normocytic normochromic anaemia and (2) TREX1 exonuclease participates in the degradation of DNA originating from erythroblast nuclei during definitive erythropoiesis. Gene expression, hematocrit, hemoglobin, immunohistochemistry (IHC) and flow cytometry were used to quantify dysfunctional erythropoiesis. An altered response to induced anaemia in the TREX1 D18N mice was determined through IHC, flow cytometry, and interferon-stimulated gene (ISG) expression analysis of the liver, spleen and erythroblastic islands (EBIs). IHC, flow cytometry, and ISG expression studies were performed in vitro to determine the role of TREX1 in the degradation of erythroblast DNA within EBIs. The TREX1 D18N mice exhibit altered erythropoiesis including a 20% reduction in hematocrit, 10–20 fold increased erythropoietic gene expression levels in the spleen and phenotypic signs of normocytic normochromic anaemia. Anaemia in TREX1 D18N mice is accompanied by increased erythropoietin (Epo), normal hepcidin levels and the TREX1 D18N mice display an inappropriate response to anaemic challenge. Enhanced ISG expression results from failed processing and subsequent sensing of undegraded erythroblast DNA in EBIs. TREX1 participates in the degradation of erythroblast DNA in the EBI and TREX1 D18N mice exhibit a normocytic normochromic anaemia.     

Parent's anxiety links household stress and young children's behavioral dysregulation

Young children rely heavily on their caregivers to gain information about the environment, especially during times of duress. Therefore, considering parental assessments of behavior in the context of stressful environments may better facilitate our understanding of the longstanding association between early environmental stressors and changes in child behavior and physiology. Confirming many previous reports, a higher degree of household stress exposure was associated with elevated mental health symptoms in 2‐ to 6‐year‐old children (N = 115; anxiety and externalizing behaviors), which were verified in a subset of children with laboratory‐based behaviors (N = 46). However, these associations were mediated by parental anxiety symptoms, which were also associated with increased cortisol levels in children. A closer look at the stressors indicated that it was the adult‐targeted, and not the child‐targeted, stressors that correlated most with children's behavior problems. These results highlight the importance of considering the mediating effect of parents, when examining associations between household stress and young children's behavioral development.     

Expectations and limitations due to brachial plexus injury: a qualitative study

Purpose

This study described physical and psychosocial limitations associated with adult brachial plexus injuries (BPI) and patients’ expectations of BPI surgery.

Methods

During in-person interviews, preoperative patients were asked about expectations of surgery and preoperative and postoperative patients were asked about limitations due to BPI. Postoperative patients also rated improvement in condition after surgery. Data were analyzed with qualitative and quantitative techniques.

Results

Ten preoperative and 13 postoperative patients were interviewed; mean age was 37 years, 19 were men, all were employed/students, and most injuries were due to trauma. Preoperative patients cited several main expectations, including pain-related issues, and improvement in arm movement, self-care, family interactions, and global life function. Work-related expectations were tailored to employment type. Preoperative and postoperative patients reported that pain, altered sensation, difficulty managing self-care, becoming physically and financially dependent, and disability in work/school were major issues. All patients reported making major compensations, particularly using the uninjured arm. Most reported multiple mental health effects, were distressed with long recovery times, were self-conscious about appearance, and avoided public situations. Additional stresses were finding and paying for BPI surgery. Some reported BPI impacted overall physical health, life priorities, and decision-making processes. Four postoperative patients reported hardly any improvement, four reported some/a good deal, and five reported a great deal of improvement.

Conclusions

BPI is a life-altering event affecting physical function, mental well-being, financial situation, relationships, self-image, and plans for the future. This study contributes to clinical practice by highlighting topics to address to provide comprehensive BPI patient-centered care.     

Do Current Recommendations for Upper Instrumented Vertebra Predict Shoulder Imbalance? An Attempted Validation of Level Selection for Adolescent Idiopathic Scoliosis

Background

Shoulder balance for adolescent idiopathic scoliosis (AIS) patients is associated with patient satisfaction and self-image. However, few validated systems exist for selecting the upper instrumented vertebra (UIV) post-surgical shoulder balance.

Questions/Purposes

The purpose is to examine the existing UIV selection criteria and correlate with post-surgical shoulder balance in AIS patients.

Methods

Patients who underwent spinal fusion at age 10–18 years for AIS over a 6-year period were reviewed. All patients with a minimum of 1-year radiographic follow-up were included. Imbalance was determined to be radiographic shoulder height |RSH| ≥ 15 mm at latest follow-up. Three UIV selection methods were considered: Lenke, Ilharreborde, and Trobisch. A recommended UIV was determined using each method from pre-surgical radiographs. The recommended UIV for each method was compared to the actual UIV instrumented for all three methods; concordance between these levels was defined as “Correct” UIV selection, and discordance was defined as “Incorrect” selection.

Results

One hundred seventy-one patients were included with 2.3 ± 1.1 year follow-up. For all methods, “Correct” UIV selection resulted in more shoulder imbalance than “Incorrect” UIV selection. Overall shoulder imbalance incidence was improved from 31.0% (53/171) to 15.2% (26/171). New shoulder imbalance incidence for patients with previously level shoulders was 8.8%.

Conclusions

We could not identify a set of UIV selection criteria that accurately predicted post-surgical shoulder balance. Further validated measures are needed in this area. The complexity of proximal thoracic curve correction is underscored in a case example, where shoulder imbalance occurred despite “Correct” UIV selection by all methods.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9451-y) contains supplementary material, which is available to authorized users.     

Influence of Zeolite Coating on the Corrosion Resistance of AZ91D Magnesium Alloy

The protective performance of zeolite coating on AZ91D magnesium alloy was evaluated using potentiodynamic polarisation and electrochemical impedance spectroscopy (EIS) in 0.1 M sodium chloride solution (NaCl). Electrical equivalent circuit (EEC) was developed based upon hypothetical corrosion mechanisms and simulated to correspond to the experimental data. The morphology and the chemical nature of the coating were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Post corrosion morphologies of the zeolite coated and the uncoated AZ91D alloy were investigated using SEM. The corrosion resistance of the zeolite coated specimen was at least one order of magnitude higher than the uncoated specimen.