Cholinergic mu-opioid receptor deletion alters reward preference and aversion-resistance.

The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT-Cre/Oprm1fl/fl) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms. Male and female ChAT-Cre/Oprm1fl/fl mice were generated and heterozygous Cre+ (knockout) and Cre- (control) mice were tested for alcohol consumption in two drinking paradigms: limited access "Drinking in the Dark" and intermittent access. Quinine was added to the drinking bottles in the DID experiment to test aversion-resistant, "compulsive" drinking. Nicotine and sucrose drinking were also assessed so comparisons could be made with other rewarding substances. Cholinergic MOR deletion did not influence consumption or preference for ethanol (EtOH) in either drinking task. Differences were observed in aversion-resistance in males with Cre + mice tolerating lower concentrations of quinine than Cre-. In contrast to EtOH, preference for nicotine was reduced following cholinergic MOR deletion while sucrose consumption and preference was increased in Cre+ (vs. Cre-) females. Locomotor activity was also greater in females following the deletion. These results suggest that cholinergic MORs participate in preference for rewarding substances. Further, while they are not required for consumption of alcohol alone, cholinergic MORs may influence the tendency to drink despite negative consequences.

Cholinergic mu-opioid receptors participate in nicotine, but not ethanol, drinking behaviors.

Heavy alcohol use and binge drinking are important contributors to alcohol use disorder (AUD). The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT-Cre/Oprm1 fl/fl ) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms. Male and female ChAT-Cre/Oprm1 fl/fl mice were generated and heterozygous Cre+ (knockout) and Cre-(control) mice were tested for alcohol and nicotine consumption. In Experiment 1, binge-like and quinine-resistant drinking was tested using 15% ethanol (EtOH) in a two-bottle, limited-access Drinking in the Dark paradigm. Experiment 2 involved a six-week intermittent access paradigm in which mice received 20% EtOH, nicotine, and then a combination of the two drugs. Deleting MORs in cholinergic cells did not alter consumption of EtOH in Experiment 1 or 2. In Experiment 1, the MOR deletion resulted in greater consumption of quinine-adulterated EtOH in male Cre+ mice (vs. Cre-). In Experiment 2, Cre+ mice demonstrated a significantly lower preference for nicotine but did not differ from Cre-mice in nicotine or nicotine + EtOH consumption. These data suggest that cholinergic MORs are involved in nicotine, but not EtOH, drinking behaviors and may contribute to aversion resistant EtOH drinking in a sex-dependent manner.

Principles for secondary traumatic stress-responsive practice: An expert consensus approach.

OBJECTIVE: Though research on secondary traumatic stress (STS) has greatly increased in the past decade, to date the field lacks a coherent set of guiding principles for practice that behavioral health providers and organizations can use to mitigate the occurrence and impact of STS. As such it is important to identify effective strategies, grounded in research and professional experience, to reduce the occurrence and impact of STS among behavioral health professionals and organizations. METHOD: We conducted a four-stage modified Delphi survey. Thirty-one international STS experts were invited to participate, with a minimum of 19 responding in each round. Thematic analysis was conducted on qualitative data, which was incorporated into revisions of the principles. RESULTS: Consensus was achieved on 14 principles, seven targeted at individual professionals, and seven targeted at organizations. CONCLUSIONS: This is the first effort to delineate principles for practice intended to reduce the occurrence and impact of STS in individual and organizational practice in behavioral health services. The principles are intended to inform best practices for individuals and organizations providing services to persons and communities who have experienced trauma and thereby improve the quality and effectiveness of services to traumatized populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Image quality and dose evaluation of MVCT TomoTherapy acquisitions: A phantom study.

BACKGROUND: The aim of this study is to evaluate the dose delivered and the image quality of pre-treatment MVCT images with Hi-Art TomoTherapy system, varying acquisition and reconstruction parameters. MATERIALS AND METHODS: Catphan 500 MVCT images were acquired with all acquisition pitch and reconstruction intervals; image quality was evaluated in terms of noise, uniformity, contrast linearity, contrast-to-noise ratio (CNR) and spatial resolution with the Modulation Transfer Function (MTF). Dose was evaluated as Multi Slice Average Dose (MSADw) and measurements were performed with the Standard TomoTherapy® Quality Assurance Kit composed by the TomoTherapy Phantom, the Exradin A1SL ion chamber and TomoElectrometer. For each pitch-reconstruction interval, acquisitions were repeated 5 times. RESULTS: Differences in noise and uniformity, though statistically significant in some cases, were very small: noise ranged from 2.3% for Coarse - 3 mm to 2.4% for Coarse - 6 mm, while uniformity passed from 99.5% for Coarse - 6 mm to 99.8% for Normal - 4 mm. No differences at all were found for CNR for high and low density inserts, while MTF was higher for pitch Coarse, even if no differences in spatial resolution were observed visually (spatial resolution was up to 4 lp/cm for all combinations of pitch and reconstruction interval). Dose was dependent on pitch, being 1.0 cGy for Coarse, 1.5 cGy for Normal and 2.85 cGy for Fine. CONCLUSIONS: We observed negligible differences in image quality among different pitch and reconstruction interval, thus, considerations regarding pre-treatment imaging modalities should be based only on dose delivered and on the desired resolution along the cranio-caudal axis for image-guided radiotherapy and adaptive radiotherapy purposes.

Case series on multiple prostate re-irradiation for locally recurrent prostate cancer: something ventured, something gained.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Impact of image guidance on toxicity and tumour outcome in moderately hypofractionated external-beam radiotherapy for prostate cancer.

To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and 12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69-77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%; P = 0.002) and more high-volume target (75% vs 60%; P < 0.001) were included. Acute gastro-intestinal (GI) toxicity G > 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI G > 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity G > 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU G > 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU > 1 (P = 0.004) and for GI > 1 (P < 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.

Oncologist use and perception of large panel next-generation tumor sequencing.

BACKGROUND: Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making. PATIENTS AND METHODS: All physicians who consented patients to MSK-IMPACT, a next-generation hybridization capture assay, in tumor types where molecular profiling is not routinely performed were asked to complete a questionnaire for each patient. Physician determination of genomic 'actionability' was compared to an expertly curated knowledgebase of somatic variants. Reported management decisions were compared to chart review. RESULTS: Responses were received from 146 physicians pertaining to 1932 patients diagnosed with 1 of 49 cancer types. Physicians indicated that sequencing altered management in 21% (331/1593) of patients in need of a treatment change. Among those in whom treatment was not altered, physicians indicated the presence of an actionable alteration in 55% (805/1474), however, only 45% (362/805) of these cases had a genomic variant annotated as actionable by expert curators. Further evaluation of these patients revealed that 66% (291/443) had a variant in a gene associated with biologic but not clinical evidence of actionability or a variant of unknown significance in a gene with at least one known actionable alteration. Of the cases annotated as actionable by experts, physicians identified an actionable alteration in 81% (362/445). In total, 13% (245/1932) of patients were enrolled to a genomically matched trial. CONCLUSION: Although physician and expert assessment differed, clinicians demonstrate substantial awareness of the genes associated with potential actionability and report using this knowledge to inform management in one in five patients. CLINICAL TRIAL NUMBER: NCT01775072.

Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease.

OBJECTIVES: To assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies. METHOD: This was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis. The mean age of trauma patients was 43 ± 19.6 years, 57 ± 11.7 years for dissection and 72 ± 9.6 years for aneurysm patients. A standardized protocol was used to measure aortic arch diameter, length, and take-off angle and clockface orientation of branch vessels. Differences in arch anatomy and length were assessed using ANOVA and independent t tests. RESULTS: Of the 210 arches evaluated, 22% had arch vessel common trunk configurations. The aortic diameter and the distance from the left main coronary (LMC) to the left common carotid (LCC) were greater in dissection patients than in trauma or aneurysm patients (p < .001). Aortic diameter in aneurysm patients was greater compared with trauma patients (p < .05). The distances from the branch vessels to the celiac artery (CA) were greater in dissection and aneurysm patients than in trauma patients (p < .001). The take-off angle of the innominate (I), LCCA, and left subclavian (LS) were greater, between 19% and 36%, in trauma patients than in dissection and aneurysm patients (p < .001). Clockface orientation of the arch vessels varies between pathologies. CONCLUSIONS: Arch anatomy has significant morphologic differences when comparing aortic pathologies. Describing these differences in a large sample of patients is beneficial for device designs and patient selection.

Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer.

OBJECTIVE: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). METHODS: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)). RESULTS: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. CONCLUSION: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. ADVANCES IN KNOWLEDGE: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Planning study to compare dynamic and rapid arc techniques for postprostatectomy radiotherapy of prostate cancer.

PURPOSE: To compare our standard technique for postprostatectomy radiotherapy of prostate cancer, i.e. using two lateral conformal dynamic arcs with volumetric-modulated arc therapy (VMAT) performed with the RapidArc(®) (Varian Medical Systems, Palo Alto, CA, USA). The plans were referred to as DA and RA, respectively. MATERIALS AND METHODS: The treatment plans of 44 patients receiving adjuvant/salvage radiotherapy in the first months of 2010 were compared. In all cases, the prescribed total dose was 66-68.2 Gy (2.2 Gy per fraction). Both DA and RA plans were optimized in terms of dose coverage and constraints. RESULTS: Small differences between the techniques were observed for planning target volume (PTV) dose distribution, whereas significant differences in sparing of organs at risk (OARs) were recorded (p < 0.0001). The OAR values (median; 95 % confidence interval, CI) were: rectum: D30 % = 60.7 Gy (59.40-62.04 Gy) and 48.2 Gy (46.40-52.72 Gy), D60 % = 34.1 Gy (28.50-38.92 Gy) and 27.7 Gy (21.80-31.51 Gy); bladder: D30 % = 57.3 Gy (45.83-64.53 Gy) and 46.4 Gy (33.23-61.48 Gy), D50 % = 16.4 Gy (11.89-42.38 Gy) and 17.2 Gy (10.97-27.90 Gy), for DA and RA, respectively. Treatment times were very similar, whereas the monitor units (MU) were 550 ± 29 versus 277 ± 3 for RA and DA, respectively. CONCLUSION: Dose-volume histograms (DVHs) show improvements in OAR sparing with RA. However, the RA technique is associated with almost double the number of MUs compared to DA. Regarding the PTV, DA is slightly superior in terms of D2 % and dose homogeneity. On the whole, the results suggest that RA be the favorable technique.

Electronic portal imaging registration in breast cancer radiotherapy verification: analysis of inter-observer agreement among different categories of health practitioners.

Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies.

Predictors of early graft failure after infrainguinal bypass surgery: a risk-adjusted analysis from the NSQIP.

INTRODUCTION AND OBJECTIVES: Infrainguinal bypass surgery (BPG) is accompanied by significant 30-day mortality and morbidity, including early graft failure. The goal of this study is to identify patient- and procedure-specific factors which predict the rate of early graft failure in contemporary practice. METHODS: Data was obtained from the private sector National Surgical Quality Improvement Program, a prospective, validated database collected between 2005 and 2008 from 211 hospitals, using primary and modifier Current Procedural Terminology codes for BPG. The primary endpoint was graft failure at 30 days. Procedural parameters, patient demographics and clinical variables were analyzed by univariate and multivariate methods. RESULTS: There were 9217 BPG procedures (limb salvage, 49%; infrapopliteal distal anastomosis, 43%; prosthetic 32%) with patient variables: age 67 ± 12 years, male 64%, diabetes 44%, dialysis 7.4%. Mortality was 2.4%, major morbidity was 17.3%, and graft failure rate was 6.3% at 30 days. Multivariate predictors of graft failure demonstrated correlation (p-value, OR) with female gender (p = 0.0054, 1.29), limb salvage indication (p < 0.0001, 1.60), infrapopliteal anastomosis (p < 0.0001, 2.15), composite graft (p = 0.0436, 1.82), current smoking (p = 0.0007, 1.36), impaired sensorium (p = 0.0075, 2.13), emergency procedure (p < 0.0001, 2.03), previous vascular procedure (p = 0.0005, 1.39), and platelets >400K (p = 0.0019, 1.49). High-risk composite constructs utilizing these significant predictive factors can identify cohorts of patients with up to a 98-fold increase in odds of early graft failure. CONCLUSIONS: These results describe common risk factors that correlate with early graft thrombosis including the unique description of its association with thrombocytosis. Additional risk factors thus identify a subset of patients who are at highest risk for early BPG failure. This data may be used to refine patient selection.

Intraprostatic fiducial markers: a potential application for ultrasound-guided radiotherapy in prostate cancer.

We report on a two-phase test performed to assess the ability of the ultrasound-based B-mode acquisition and targeting (BAT) trans-abdominal system to identify non-dedicated fiducial markers implanted into the prostate gland for subsequent image-guided radiotherapy.Although further investigation is warranted in order to identify the optimal echogenic marker and to define its potential use for image-guided radiotherapy in prostate cancer patients, we demonstrate the feasibility of the BAT system for the visualization of non-ultrasound-dedicated markers.

Mental disorders and request for psychiatric intervention in an Italian local jail.

The issue of the prevalence of psychiatric illnesses in Italian prison samples has not received the same attention paid at an international level. The aims of the present study were to evaluate the prevalence of psychiatric disorders diagnosed according to DSM-III-R criteria among an Italian prisoner population, and to examine prisoners' requests for psychiatric intervention in relationship to the presence or absence of different psychiatric disorders. One hundred forty-two Italian male subjects from the Casa Circondariale of Messina, Italy, were evaluated using the Structured Clinical Interview for DSM-III-R Non-Patient Version - SCID I and SCID II. A very high rate of disorders was found among inmates: 85.2% (n=121) of the sample were affected by a psychiatric disorder. Of the total sample, 51.4% (n=73) had requested psychiatric treatment during detention. The detection, diagnosis and treatment of the mentally ill prisoners is a primary goal for a better organization of services and prison settings; screening procedures for evaluating the presence of psychiatric disorders, with the aim to promote differential strategies for the care and rehabilitation of inmates, are needed.

Genetic evolutionary taboo search for optimal marker placement in infrared patient setup.

In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study.

Based on the evidence that lamotrigine added to clozapine in refractory schizophrenic patients has reported promising results, the present 24-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 200 mg/day of lamotrigine or a placebo. A final sample of fifty-one patients completed the study. The results obtained indicate that lamotrigine added to stable clozapine treatment showed a beneficial effect on the negative, positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients. Regarding cognitive functions, improvement was observed in some explored areas, such as attentional resistance to interference, verbal fluency and executive functioning. The findings provide evidence that lamotrigine augmentation of clozapine treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant schizophrenia.

[Comparation of levels of anxiety and depression in patients with autoimmune and chronic-degenerative rheumatic: preliminary data]. / Comparazione dei livelli di ansia e depressione in soggetti affetti da patologie reumatiche su base autoimmune e cronico-degenerative: dati preliminari.

UNLABELLED: Scientific research on rheumatic diseases was often focused on the link between psychological features and disease. Depression and anxiety are frequently observed with an higher incidence among rheumatic patients in comparison to general population. In autoimmune diseases, such as rheumatoid arthritis, an important role for psychiatric symptoms could be played by the alteration of cytokines levels. In the chronic-degenerative diseases, psychological factors such as stress and depression, can be involved in perception of pain. OBJECTIVE: We aimed at evaluating in a sample of 50 patients (25 with rheumatoid arthritis and 25 with osteoarthritis) levels of pain, anxiety and depression. METHODS: We evaluated two group of patients with rheumatic disease, group A (25 with Rheumatoid Arthritis, mean age = 45.1; DS =15.24) and group B (25 with osteoarthritis, mean age = 54.3; DS =14.74) by clinic examination and with the following tests, SF-MPQ, HAQ, HAM-A, HAM-D. RESULTS: We found in group A higher levels of depression and anxiety but lower levels of pain, which was more expressed in group B. CONCLUSION: Depression and anxiety were observed with an higher prevalence in patients with autoimmune disease, whereas pain was stronger in patients with osteoarthritis, a degenerative disease. We could explain this phenomenon considering the aetiopathology of the two conditions. As regard to autoimmune disorders, these symptoms may reflect the direct effect of cytokines on the central nervous system. As far as it concerns chronic-degenerative diseases, anxiety and depression are usually considered "reactive" to pain, not "constitutive".

PECAM-1/IgG attenuates peroxynitrite-mediated extremity reperfusion injury.

OBJECTIVE: Neutrophil transendothelial migration, a key feature of skeletal muscle ischemia and reperfusion (I/R) injury, is mediated by the platelet endothelial cell adhesion molecule-1 (PECAM-1). Peroxynitrite anion, a toxic product of neutrophil superoxide anion and nitric oxide, contributes to oxidative skeletal muscle injury and can be quantified by measurement of protein tyrosine nitration after I/R. This study hypothesizes that administration of the PECAM-1/IgG antibody chimera will inhibit peroxynitrite-mediated injury after I/R. METHODS: The study was composed of five groups: an I/R group (n = 4), a sham treatment group anesthetic control (n = 3), a treatment group receiving the PECAM-1/immunoglobulin G (IgG) antibody chimera with I/R (n = 9), a treatment group receiving human IgG with I/R as an antibody control (n = 6), and a treatment group receiving normal saline solution with I/R as a vehicle control (n = 5). The right hind limb in male New Zealand white rabbits was rendered ischemic by occluding the iliac and femoral arteries for 3 hours, followed by 2 hours of reperfusion (I/R). Sham-treated rabbits underwent arterial dissection without arterial occlusion. PECAM-1/IgG-treated rabbits and IgG-treated rabbits received an infusion of 1 mg/kg in normal saline solution 20 mL via an ear vein catheter during the last 5 minutes of ischemia and the first 15 minutes of reperfusion. Saline solution-treated rabbits similarly received normal saline solution 20 mL. The anterior tibialis muscle was harvested after reperfusion. Immunohistochemical staining for nitrotyrosine was performed with monoclonal antinitrotyrosine antibodies and fluorescently labeled secondary antibodies. Computed morphometric study was performed to calculate relative fluorescence scores for each histologic section. Averaged fluorescence scores were analyzed by one-way analysis of variance with Bonferroni post hoc comparison. RESULTS: The averaged fluorescence scores (mean +/- SEM) for the sham-treated (2.88 +/- 0.78) and PECAM-1/IgG-treated (6.16 +/- 0.43) groups demonstrated a significant reduction in quantitative fluorescence compared with the IgG- (15.17 +/- 2.01) and saline solution-treated (17.46 +/- 3.71) control groups, and the I/R-treated (18.52 +/- 3.00) group, (P <.05). CONCLUSIONS: These results suggest that PECAM-1/IgG diminishes peroxynitrite-mediated oxidative skeletal muscle injury by inhibiting neutrophil transendothelial migration and may therefore prove a useful therapeutic agent in the treatment of reperfusion injury.