Factors explaining variance in perceived pain in women with fibromyalgia

BACKGROUND: We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain. METHODS: Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge. RESULTS: Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain. CONCLUSION: Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients

Psychometric properties of the Dutch Five Facet Mindfulness Questionnaire (FFMQ) in patients with fibromyalgia

Mindfulness-based interventions are increasingly being used in clinical populations to reduce psychological distress and improve functioning. The Five Facet Mindfulness Questionnaire (FFMQ) is a questionnaire that measures five facets of mindfulness: observe, describe, actaware, nonjudge and nonreact. The goal of this study was to examine the psychometric properties of the FFMQ in a clinical population of fibromyalgia patients. A total of 141 patients completed an online questionnaire on mindfulness (FFMQ) and theoretically related (e.g. acceptance, openness, alexithymia) and unrelated (physical health) constructs. Thirty-eight patients filled in the FFMQ twice. A confirmatory factor analysis (CFA) was conducted to test the five-factor structure of the FFMQ. Internal consistency and test–retest reliability were respectively assessed with Cronbach’s α and intraclass correlation coefficients. Construct validity was examined by correlating FFMQ facets with theoretically related and unrelated constructs. Incremental validity in predicting mental health and psychological symptoms was examined with regression analyses. CFA confirmed the correlated five-factor structure of the FFMQ. Internal consistency of the five facets was satisfactory and test–retest reliability was good to excellent. Construct validity was excellent, as shown by the moderate to large correlations with related constructs (except observe facet) and weak correlation with a theoretically unrelated construct. Two of the five facets (actaware and nonjudge) had incremental validity over the others in predicting mental health and psychological symptoms. After controlling for related constructs, the actaware facet remained a significant predictor. This study showed satisfactory psychometric properties of the Dutch FFMQ in fibromyalgia patients. The observe facet, however, should be used with caution given its deviant relationship with theoretically related constructs

Gamma probes and their use in tumor detection in colorectal cancer

The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

AbstractBackgroundFor patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.MethodsFifty-eight patients with three (2–7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2doses×3, plus gemcitabine, weekly 200mg/m2 doses×4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.ResultsCytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year.ConclusionsClinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting

Accurate path integration in continuous attractor network models of grid cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10–100 meters and ~1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other

A Signature of Maternal Anti-Fetal Rejection in Spontaneous Preterm Birth: Chronic Chorioamnionitis, Anti-Human Leukocyte Antigen Antibodies, and C4d

Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth.This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29–28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60–21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42–114.66) were associated with preterm labor and delivery.A major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions