Articles: human.
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Preclinical studies show that opioids stimulate angiogenesis and tumor progression through the mu opioid receptor (MOR). Although MOR is overexpressed in several human malignancies, the effect of chronic opioid requirement on cancer progression or survival has not been examined in humans. ⋯ Higher MOR expression and greater opioid requirement are associated with shorter progression-free survival and overall survival in patients with metastatic prostate cancer. Nevertheless, clinical practice should not be changed until prospective randomized trials show that opioid use is associated with inferior clinical outcomes, and that abrogation of the peripheral activities of opioids ameliorates this effect.
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Sleep and headache have both generated curiosity within the human mind for centuries. The relationship between headache and sleep disorders is very complex. While Lieving in 1873 first observed that headaches were linked to sleep, Dexter and Weitzman in 1970 described the relationship between headache and sleep stages. ⋯ Patient education and lifestyle modification play a significant role in overall success of the treatment. Chronic tension-type headache and chronic migraine have high prevalence of insomnia and comorbid psychiatric disorders, which require behavioral insomnia treatment and medication if needed along with psychiatric evaluation. Apart from the abortive treatment tailored to the headache types, - such as triptans and DHE 45 for migraine and nonsteroidal anti-inflammatory medication for chronic tension-type headache, preventive treatment with different class of medications including antiepileptics (Topamax and Depakote), calcium channel blockers (verapamil), beta blockers (propranolol), antidepressants (amitriptyline), and Botox may be used depending upon the comorbid conditions.
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Despite the significant interest in the assessment of human cerebral perfusion, investigations into human spinal cord perfusion (SCP) are scarce. Current intraoperative monitoring of spinal cord relies on the assessment of neural conduction as a surrogate for SCP. However, there are various inherent limitations associated with the use of these techniques. Near infrared spectroscopy (NIRS) has been successfully used for monitoring and assessment of human cerebral perfusion and has shown promising results in intraoperative assessment of SCP in animal models. ⋯ Intraoperative NIRS with ICG tracer technique can identify an increase in the SCP in response to hypercapnia. It is possible to use this technique for monitoring SCP over the dura and the lamina. This technique could potentially be used to provide insight in to the pathophysiology and autoregulation of commonly acquired spinal cord conditions. Further research assessing the use of NIRS for monitoring of SCP is required.
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Neurobiology of aging · Dec 2013
Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.
Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. ⋯ The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant.
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Am. J. Physiol. Lung Cell Mol. Physiol. · Nov 2013
Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids.
Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0-80 min and 24 h after IPFT with scuPA (0-0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. ⋯ Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications.