Pain associated with specific anxiety and depressive disorders in a nationally representative population sample

Objective  

To examine in a nationally representative sample (a) the differential association of specific anxiety and depressive disorders defined according to DSM-IV with pain disorder (PD) and pain symptoms, and (b) whether pain-associated anxiety and depressive disorders and their comorbidity have different implications in terms of impairment, disability, health care utilization, and substance use.     

Comparison of analytical mathematical approaches for identifying key nuclear magnetic resonance spectroscopy biomarkers in the diagnosis and assessment of clinical change of diseases

Nuclear magnetic resonance (NMR) spectroscopy is a rapidly emerging technology that can be used to assess tissue metabolic profile in the living animal. At the present time, no approach has been developed 1) to systematically identify profiles of key chemical alterations that can be used as biomarkers to diagnose diseases and to monitor disease progression; and 2) to assess mathematically the diagnostic power of potential biomarkers. To address this issue, we have evaluated mathematical approaches that employ receiver operating characteristic (ROC) curve analysis, linear discriminant analysis, and logistic regression analysis to systematically identify key biomarkers from NMR spectra that have excellent diagnostic power and can be used accurately for disease diagnosis and monitoring. To validate our mathematical approaches, we studied the striatal concentrations of 17 metabolites of 13 R6/2 transgenic mice with Huntington's disease, as well as those of 17 wild-type (WT) mice, which were obtained via in vivo proton NMR spectroscopy (9.4 Tesla). We developed diagnostic biomarker models and clinical change assessment models based on our three aforementioned mathematical approaches, and we tested all of them, first, with the 30 original mice and, then, with 31 unknown mice. Their prediction results were compared with genotyping-the gold standard. All models correctly diagnosed all of the 30 original mice (17 WT and 13 R6/2) and all of the 31 unknown mice (20 WT and 11 R6/2), with a positive likelihood ratio approximating infinity [1/0 (→ ∞)], and with a negative likelihood ratio equal to zero [0/1 = 0].     

Prophylactic embolization of hepatic artery pseudoaneurysm after blunt abdominal trauma in a child

We describe a 10-year-old boy who developed a pseudoaneurysm in the territory of the left hepatic artery after blunt trauma to the abdomen, which was prophylactically embolized. He was discharged early and was able to return to activities of daily life. In view of the potentially fatal complication of severe hemorrhage from a missed hepatic pseudoaneurysm rupture, recognition and early embolization of a traumatic pseudoaneurysm of hepatic artery are recommended. This decreases morbidity, mortality, and length of hospital stay and allows for early mobilization especially in children who are difficult to restrain in bed.     

Folate receptor overexpression is associated with poor outcome in breast cancer

The high affinity folate receptor is a membrane-associated glycoprotein that is preferentially expressed in cancers of epithelial origin and rarely expressed in normal cells. We examined its expression pattern in breast cancer, utilizing a tissue microarray containing samples from 63 invasive breast cancers from women with divergent clinical outcomes. Thirty-three women comprised the poor outcome group with a median time to recurrence of 1.9 years. Thirty women, the good outcome group, were free of recurrence for a minimum of 7 years after diagnosis. The intensity of folate receptor staining was strongly correlated with outcome. There were two summary categories of staining intensity: weak (n = 42) or strong (n = 21). In the strong staining group, 17 of 21 women (81%) have recurred and their median survival is 2.4 years. In the weak staining group, 16 of 42 women (38%) have recurred. Their median survival is not estimable. After adjustment for tumor size, nodal status, ER status, adjuvant therapy, histology and tumor grade, strong staining for the folate receptor remained significantly associated with poor outcome, p < 0.001. Our work requires validation in a larger cohort, but supports the possibility of using folate receptor-targeted approaches in the management of breast cancer.     

Derivation of stable microarray cancer-differentiating signatures using consensus scoring of multiple random sampling and gene-ranking consistency evaluation

Microarrays have been explored for deriving molecular signatures to determine disease outcomes, mechanisms, targets, and treatment strategies. Although exhibiting good predictive performance, some derived signatures are unstable due to noises arising from measurement variability and biological differences. Improvements in measurement, annotation, and signature selection methods have been proposed. We explored a new signature selection method that incorporates consensus scoring of multiple random sampling and multistep evaluation of gene-ranking consistency for maximally avoiding erroneous elimination of predictor genes. This method was tested by using a well-studied 62-sample colon cancer data set and two other cancer data sets (86-sample lung adenocarcinoma and 60-sample hepatocellular carcinoma). For the colon cancer data set, the derived signatures of 20 sampling sets, composed of 10,000 training test sets, are fairly stable with 80% of top 50 and 69% to 93% of all predictor genes shared by all 20 signatures. These shared predictor genes include 48 cancer-related and 16 cancer-implicated genes, as well as 50% of the previously derived predictor genes. The derived signatures outperform all previously derived signatures in predicting colon cancer outcomes from an independent data set collected from the Stanford Microarray Database. Our method showed similar performance for the other two data sets, suggesting its usefulness in deriving stable signatures for biomarker and target discovery.     

Association of N-type calcium channel autoimmunity in patients with autoimmune autonomic ganglionopathy

The nicotinic acetylcholine receptor (nAChR) antibody directly contributes to the autonomic dysfunction in Autoimmune Autonomic Ganglionopathy (AAG). The pathological mechanism leading to autonomic dysfunction in seronegative AAG is unclear. We evaluated patients with presumed antibody negative AAG (n = 49) to determine whether there was an association with other autoantibodies. Three patients met the clinical criteria and were positive for N-type calcium channel antibodies. All patients had severe autonomic dysfunction characterized by orthostatic hypotension and gastrointestinal involvement. Autonomic testing revealed severe impairment of sudomotor, cardiovagal, and adrenergic domains. These findings raise the possibility that other autoantibodies may contribute to the pathogenesis of AAG.     

Pathological crying caused by high-frequency stimulation in the region of the caudal internal capsule

BACKGROUND: Pathological crying has been rarely reported after deep brain stimulation. The exact neural substrate is unknown, but it is often assumed that pathological crying and the pseudobulbar syndrome result from disturbances of a common neural pathway. DESIGN: Case report. SETTING: Tertiary referral center for neurosurgery. Patient A 48-year-old woman with advanced Parkinson disease who received bilateral implantation of deep brain stimulators in her subthalamic nuclei. RESULTS: Stimulation in the region of the caudal internal capsule resulted in pathological crying but no other features of pseudobulbar palsy. CONCLUSIONS: At least 1 of the pathways controlling crying passes through the region of the caudal internal capsule, and this pathway is distinct from those involved with laughter and nonemotional facial movements. Moreover, different stimulation frequencies may elicit either crying or anxiety but not both.     

Immunolocalization of NMDA receptor subunit NR3B in selected structures in the rat forebrain, cerebellum, and lumbar spinal cord

N-methyl-D-aspartate (NMDA) receptors have been implicated in many neurological disorders. Although NMDA receptors are best known for their high calcium permeability, the recently discovered NR3 subunits, NR3A and NR3B, have been shown to reduce the calcium permeability of the NMDA receptor. Thus, NR3 subunits may be important players in modulating synaptic plasticity in neurons. Although NR3B expression in the rodent and human brain has been studied, little is known about its distribution in different cell types. Here we used immunolabeling with a specific NR3B antibody together with antibodies against established neurochemical markers to determine the cellular and subcellular localization of NR3B. The nucleus was concurrently stained with NR3B immunolabeling to show that NR3B is widely expressed by many cells in each brain region. Our findings indicate that NR3B is widely expressed in the structures examined in the rat forebrain (hippocampus, cerebral cortex, caudoputamen, and nucleus accumbens), cerebellum, and lumbar sections of the spinal cord. Within these regions NR3B was found to be expressed in all the substructures of the hippocampus (CA1, CA3, dentate gyrus), the various layers of the cerebral cortex, projection neurons and interneurons of the striatum, different cell types of the cerebellum, and motor neurons of the spinal cord. Furthermore, when stained with NR1-the obligatory subunit responsible for forming functional NMDA receptors-the distribution of NR3B appears to be as ubiquitous as NR1. Taken together, our data suggest that there may be a population of NR3B-containing NMDA receptors conferring new functional roles in the mammalian central nervous system.     

Management of neurogenic orthostatic hypotension: an update

Orthostatic hypotension (OH) is common in elderly people and in patients with disorders such as diabetes and Parkinson's disease. Grading of the severity of OH and its effect on the patient's quality of life are important. The symptoms vary with orthostatic stress, and subtle symptoms such as tiredness and cognitive impairment should be recognised. Standard drug treatment for OH is effective but worsens supine hypertension, whereas pyridostigmine can improve OH slightly but significantly without worsening of supine hypertension. Because orthostatic stress varies from moment to moment and drug treatment is suboptimal, drug treatment of OH needs to be combined with non-pharmacological approaches, such as compression of venous capacitance beds, use of physical counter-manoeuvres, and intermittent water-bolus treatment.