Relationship of lower extremity skin blood flow to the ankle brachial index in patients with peripheral arterial disease and normal volunteers

Changes in posture of the lower extremities induce changes in skin blood flow, known as veno-arteriolar response (VAR). We investigated the relationship between ankle brachial index (ABI) and VAR in patients (ABI<0.9) with peripheral arterial disease (PAD) and age-matched normal controls (ABI>1). We measured ankle pressure, ABI at rest, and post-exercise ABI. Using laser Doppler flowmetry, skin blood flow was measured with the lower extremity in extended and flexed positions and the fractional change (extended-flexed/extended) in blood flow (VAR) was calculated. With external pressure applied serially to the lower extremity in the extended position using a sphygmomanometer, the pressure (PVAR) at which the VAR was similar to that in the flexed position was recorded. Patients and controls did not differ by age or comorbidity, except higher cigarette smoking in patients (95.8% vs. 4.3%, p=0.001). VAR and PVAR were significantly lower in patients than controls (0.42+/-0.16 vs. 0.65+/-0.11 flux/min, p=0.001 and 29+/-8 vs. 48+/-9 mm Hg, p=0.001, respectively). There was significant correlation between ABI-post and VAR (r=0.6, p=0.01) and between the VAR and PVAR (r=0.8, p=0.001). VAR<0.3 flux/min was 100% sensitive, 80% specific, and area under curve of 0.88, p=0.001 for detecting PAD as defined by ABI<0.9. Similarly, PVAR of 22 mm Hg was 100% sensitive, 85% specific, and area under curve of 0.94, p=0.001 for detecting PAD. Skin blood flow by this method correlates with the presence and severity of an abnormal ABI. This may offer a method of monitoring the effect of therapy and regression of peripheral atherosclerosis.     

Lymphoid progenitors in normal mouse lymph nodes develop into NK cells and T cells in vitro and in vivo

We have identified a population of normal mouse LN cells, termed LN lymphoid progenitor (LNLP), resembling common lymphoid progenitor (CLP) in the bone marrow. LNLPs lack lineage markers and express CD127, low levels of CD117 (c-Kit), and Sca-1, but lack fms-related tyrosine kinase 3. They efficiently differentiate in vitro into natural killer (NK) cells and T cells, but not mature B cells. LNLPs injected into nonirradiated lymphopenic mice that have no LN develop into mostly splenic T cells with low numbers of NK cells and B cells. When injected into irradiated mice, they generate NK cells and T cells, but not B cells, in the LN. By contrast, bone marrow CLPs develop into mostly B cells with very small numbers of T and NK cells in recipients' spleen and LN. LNLPs have NK and T-cell potentials, but little B-cell potential, and they can develop into NK cells within the LN of normal mice, but their contribution to the T-cell lineage is unknown.     

Age-related differences in the prevalence and correlates of anxiety in youth with autism spectrum disorders

Age-related differences in the prevalence and correlates of anxiety were cross-sectionally examined in 1316 children and adolescents with autism spectrum disorder (ASD) who presented for initial evaluation at 14 outpatient autism centers around the country and in Canada. The prevalence of clinical and subclinical anxiety as well as the correlates of anxiety were examined in three age groups of children: preschool, school age and adolescents. Findings showed that the prevalence of anxiety in each age group exceeded the prevalence of anxiety in the general population. Adolescents and school age children had the highest prevalence of clinical (40%) and subclinical anxiety (26%), respectively. Higher IQ and less ASD severity were each weakly correlated with more anxiety in preschool and school age children. Affective symptoms were strongly associated with anxiety in each age group. Age specific psychiatric comorbidities were also present. Anxiety was associated with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in the preschool group, ODD and somatic symptoms in the school age children, and ADHD symptoms in adolescents. These data underscore the need for prevention and treatment of anxiety as well as research examining the characteristics of anxiety in children with ASD using a developmental framework.     

HRQoL after coronary artery bypass grafting and percutaneous coronary intervention for stable angina

Objectives. To assess the health related quality of life (HRQoL) and the change in the NYHA class after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the management of stable coronary artery disease (CAD). The study was non-randomized. CABG group consisted of 240 patients and 229 patients were treated with PCI. HRQoL was measured prospectively by the 15D instrument. Results. Three-year survival was 95.0 and 95.6% (NS). The HRQoL improved statistically in both groups until 6 months after treatment but deteriorated towards the end of the follow-up of 36 months. Clinically evident improvement of the HRQoL and decrease of the NYHA class took place more frequently among CABG patients. Conclusions. Despite initially more serious preoperative state and more demanding procedure CABG patients achieve equal level of HRQoL when compared with PCI patients. CABG patients may also obtain better relief from symptoms in mid-term follow-up. HRQoL cannot be the only factor to determine outcome after invasive treatment of CAD but it has to be placed in the context of the overall situation.     

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC_[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC_[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.     

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

For weeks after primary immunization with thymus-dependent antigens the responding lymph nodes contain effector CD4 T cells in T zones and germinal centers as well as recirculating memory T cells. Conversely, remote nodes, not exposed to antigen, only receive recirculating memory cells. We assessed whether lymph nodes with follicular effector CD4 T cells in addition to recirculating memory CD4 T cells mount a more rapid secondary response than nodes that only contain recirculating memory cells. Also, the extent to which T cell frequency governs accelerated CD4 T cell recall responses was tested. For this, secondary antibody responses to a superantigen, where the frequency of responding T cells is not increased at the time of challenge, were compared with those to conventional protein antigens. With both types of antigens similar accelerated responses were elicited in the node draining the site of primary immunization and in the contralateral node, not previously exposed to antigen. Thus recirculating memory cells are fully capable of mounting accelerated secondary responses, without the assistance of CD4 effector T cells, and accelerated memory responses are not solely dependent on higher T cell frequencies. Accelerated memory CD4 T cell responses were also seen in B cell-deficient mice.     

Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus,exploring novel neuroimaging diagnostics

Neurosurgical Review - As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of...