Reductions in arterial stiffness with weight loss in overweight and obese young adults: Potential mechanisms

ObjectiveArterial stiffness decreases with weight loss in overweight/obese young adults. We aimed to determine the mechanisms by which this occurs.MethodsWe evaluated carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) in 344 young adults (23% male, BMI 25–40 kg/m²) at baseline, 6, and 12 months in a behavioral weight loss intervention. Linear mixed models were used to evaluate associations between weight loss and arterial stiffness and to examine whether improvements in obesity-related factors explained these associations.ResultsAt 6 months (7% mean weight loss), there was a significant median decrease of 47.5 cm/s in cfPWV (p < 0.0001) and a mean decrease of 11.7 cm/s in baPWV (p = 0.049). At 12 months (6% mean weight loss), only cfPWV remained reduced. In models adjusting for changes in mean arterial pressure and obesity-related factors, changes in BMI (p = 0.01) and common carotid artery diameter (p = 0.003) were positively associated with change in cfPWV. Reductions in heart rate (p < 0.0001) and C-reactive protein (p = 0.02) were associated with reduced baPWV and accounted for the association between weight loss and reduced baPWV.ConclusionsWeight loss is associated with reduced cfPWV independently of changes in established hemodynamic and cardiometabolic risk factors, but its association with reduced baPWV is explained by concurrent reductions in heart rate and inflammation.     

Stroke management: updated recommendations for treatment along the care continuum

The Australian Clinical Guidelines for Stroke Management 2010 represents an update of the Clinical Guidelines for Stroke Rehabilitation and Recovery (2005) and the Clinical Guidelines for Acute Stroke Management (2007). For the first time, they cover the whole spectrum of stroke, from public awareness and prehospital response to stroke unit and stroke management strategies, acute treatment, secondary prevention, rehabilitation and community care. The guidelines also include recommendations on transient ischaemic attack. The most significant changes to previous guideline recommendations include the extension of the stroke thrombolysis window from 3 to 4.5 h and the change from positive to negative recommendations for the use of thigh-length antithrombotic stockings for deep venous thrombosis prevention and the routine use of prolonged positioning for contracture management.     

Early and Late Presentations of Graft Arterial Pseudoaneurysm Following Pancreatic Transplantation

Background

Graft pseudoaneurysm (PSA) following pancreatic transplantation (PT) is a rarely reported complication that has significant morbidity and mortality. Few case reports and small series of this complication exist.

Methods

Retrospective review of files of 106 patients who underwent PT at the Tel-Aviv Sourasky Medical center between 1995 and 2010. Accessible asymptomatic patients (n = 35) were referred for graft PSA screening using ultrasound-Doppler.

Results

Eight patients developed graft PSA (8 %). All had early posttransplant sepsis. PSA incidence among patients who had perioperative sepsis is 13 %. Three patients developed early postoperative PSA, presenting as massive abdominal bleeding requiring urgent laparotomy and graft resection. Five patients were diagnosed with late-onset graft PSA between 3 months and 11 years posttransplant: clinical presentations were massive gastrointestinal bleeding (n = 2), acute renal failure (n = 1), and asymptomatic finding on screening ultrasound-Doppler (n = 2, 6 % of screened patients).

Conclusions

PSA following PT occurs in 8 % of patients. Perioperative infection is a risk factor. Early PSAs present as massive intra-abdominal bleeding. PSA may develop years posttransplant, may be asymptomatic, but late rupture is possible and presents as gastrointestinal bleeding. We recommend screening of patients at risk with ultrasound Doppler for early detection and treatment of asymptomatic PSAs.     

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal–Wallis tests were used to compare staining scores (intensity × percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (ρ) in all cases, and stratified by HPV status. HPV-negative HNSCC over-expressed EGFR [median (range): 30 (0–300)] relative to HPV-positive HNSCC [7.5 (0–200)] (P = 0.006). VEGF and NOTCH1 were unrelated to HPV status (P > 0.05). EGFR was associated with VEGF in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive HNSCC (ρ = 0.25, P = 0.20). NOTCH1 and VEGF were associated in HPV-negative (ρ = 0.40, P = 0.01) but not HPV-positive tumors (ρ = −0.12, P = 0.57). NOTCH1 was not associated with EGFR (P > 0.05). Our results are suggestive of heterogeneity in HNSCC angiogenesis. Future studies should explore angiogenesis mechanisms in HPV-positive and HPV-negative HNSCC.

Electronic supplementary material

The online version of this article (doi:10.1007/s12105-013-0447-y) contains supplementary material, which is available to authorized users.     

Pentoxifylline and propentofylline prevent proliferation and activation of the mammalian target of rapamycin and mitogen activated protein kinase in cultured spinal astrocytes

Astrocyte activation is an important feature in many disorders of the central nervous system, including chronic pain conditions. Activation of astrocytes is characterized by a change in morphology, including hypertrophy and increased size of processes, proliferation, and an increased production of proinflammatory mediators. The xanthine derivatives pentoxifylline and propentofylline are commonly used experimentally as glial inhibitors. These compounds are generally believed to attenuate glial activity by raising cyclic AMP (cAMP) levels and inhibiting glial tumor necrosis factor (TNF) production. In the present study, we show that these substances inhibit TNF and serum‐induced astrocyte proliferation and signaling through the mammalian target of rapamycin (mTOR) pathway, demonstrated by decreased levels of phosphorylated S6 kinase (S6K), commonly used as a marker of mTOR complex (mTORC) activation. Furthermore, we show that pentoxifylline and propentofylline also inhibit JNK and p38, but not ERK, activation induced by TNF. In addition, the JNK antagonist SP600125, but not the p38 inhibitor SB203580, prevents TNF‐induced activation of S6 kinase, suggesting that pentoxifylline and propentofylline may regulate mTORC activity in spinal astrocytes partially through inhibition of the JNK pathway. Our results suggest that pentoxifylline and propentofylline inhibit astrocyte activity in a broad fashion by attenuating flux through specific pathways. © 2012 Wiley Periodicals, Inc.