Morphologic predictors of aortic expansion in chronic type B aortic dissection.

AIM To identify morphologic factors affecting aortic expansion in patients with uncomplicated type B aortic dissections. METHODS Computed tomography data of 24 patients (18 male; median age: 61 years), diagnosed with acute uncomplicated type B aortic dissections between 2002 and 2013, were retrospectively reviewed. All patients had at least two computed tomography angiography scans and six months of uneventful follow-up. Computed tomography scans were assessed by two independent readers with regard to presence and number of entry tears. Thoracic and abdominal aortic diameters were derived using image processing software. RESULTS Twenty-two of 24 patients showed aortic expansion over a median computed tomography angiographic follow-up of 33.2 months. Annual rates showed an increase of 1.7 mm for total aortic diameter, 2.1 mm for the false and a decrease of -0.4 mm for the true lumen. In three patients (12.5%), aortic diameter exceeded 60 mm during follow-up, and all three patients underwent thoracic endovascular aortic repair. Patients with a maximum aortic diameter <4 cm at baseline showed a significantly higher expansion rate compared to cases with an initial maximum aortic diameter of ≥4 cm (p=0.0471). A median of two entries (range: 1-5) was recognized per patient. Presence of more than two entry tears (n = 13) was associated with faster overall diameter expansion (mean annual rates: 2.18 mm vs. 1.16 mm; p = 0.4556), and decrease of the cross-sectional surface of the true lumen over time (annual rate for > 2 entries vs. ≤2 entries: -7.8 mm(2) vs. +37.5 mm(2); p = 0.0369). Median size of entry tears was 12 mm (range: 2-53 mm). CONCLUSIONS The results presented herein suggest that uncomplicated type B aortic dissection patients with more than two entry tears and/or an initial maximum aortic diameter of<4 cm are at risk for aortic dilatation and, therefore, may require stricter follow-up including the possible need for early intervention.

Blood-oxygen-level-dependent (BOLD) signal changes in total cortex and subcortex, pain, reward, and vigilance regions during mechanical pressure pain after morphine administration

Morphine is the most common clinical choice in the management of severe pain. Although the molecular mechanisms of morphine have already been characterized, the cerebral circuits by which it attenuates the sensation of pain have not yet been studied in humans. The objective of this two-arm (morphine versus placebo), between-subjects study was to examine whether morphine affects pain via pain-related cortical circuits, but also via reward regions that relate to the motivational state, as well as prefrontal regions that relate to vigilance as a result of morphine's sedative effects. Cortical activity was measured by the blood-oxygen-level-dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI). ^ The novelty of this study is at three levels: (i) to develop a methodology that will assess the average BOLD signal across subjects for the pain, reward, and vigilance cortical systems; (ii) to examine whether the reward and/or sedative effects of morphine are contributing factors to cortical regions associated with the motivational state and vigilance; and (iii) to propose a neuroanatomical model related to the opioid-sensitive effects of reward and sedation as a function of cortical activity related to pain in an effort to assess future analgesics. ^ Consistent with our hypotheses, our findings showed that the decrease in total pain-related volume activated between the post- and the pre-treatment morphine group was about 78%, while the post-treatment placebo group displayed only a 5% decrease when compared to pre-treatment levels of activation. The volume increase in reward regions was 451% in the post-treatment compared to the pre-treatment morphine condition. Finally, the volumetric decrease in vigilance regions was 63% in the posttreatment compared to the pre-treatment morphine condition. ^ These findings imply that changes in the blood flow of the reward and vigilance regions may be contributing factors in producing the analgesic effect under morphine administration. Future studies need to replicate this study in a higher resolution fMRI environment and to assess the proposed neuroanatomical model in patient populations. The necessity of pain research is apparent, since pain cuts across different diseases especially chronic ones, and thus, is recognized as a vital public health developing area. ^

Influence of rurality, deprivation and distance from clinic on uptake in men invited for abdominal aortic aneurysm screening

Acknowledgements This study received no specific funding. The study involved the analysis of data collected routinely as part of the national AAA screening programme in Scotland.

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions

Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation. Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of “dark neurons,” is associated with both chronic constriction injury and morphine tolerance. A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.

Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway

Rearrangements of the high mobility group protein I-C (HMGI-C) gene, consisting in the loss of the carboxyl-terminal tail, have been frequently detected in benign human tumors of mesenchymal origin. We have previously demonstrated that transgenic (TG) mice carrying a truncated HMGI-C construct (HMGI-C/T) exhibit a giant phenotype together with a predominantly abdominal/pelvic lipomatosis. Here, we report that HMGI-C/T TG mice develop natural killer (NK)-T/NK cell lymphomas starting from 12 months of age. We found an increased expression of IL-2 and IL-15 proteins and their receptors in these lymphomas, and we demonstrate that HMGI-C/T protein positively regulates their expression in vitro. Therefore, the HMGI-C/T-mediated chronic stimulation of the IL-2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMGI-C/T TG mice.

Groove pancreatitis a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Post-Operative Pain Scores and Level of Regional Anesthesia Expertise: Using Clinical Outcomes to Assess Procedural Proficiency

Background and Objectives: Peripheral nerve blockade requires regional anesthesia skills that trainees learn in several formats. Technical proficiency has shifted from a quota to comprehensive procedural evaluation. Successful nerve blockade is the clinical endpoint validating proficiency but patient, technical and procedural factors influence this result. The purpose of this study was to determine if procedural expertise for sciatic nerve blockade influenced postoperative pain scores and opioid requirements and if patient factors, technique and repetition influenced this outcome. Method: Sciatic nerve blockade by nerve stimulation and ultrasound guidance and training level of the resident performing the procedure were recorded. Patient obesity, trauma, chronic pain, opioid use and preoperative pain scores were compared to post-procedure pain scores and opioid analgesic requirements. Results: 102 patients received sciatic nerve blockade from 47 trainees over a 36 month interval. A significant relation between training level and improved pain scores was not demonstrated but transition from nerve stimulation to ultrasound guidance lowered scores in all groups. Nerve blockade failure was frequent with chronic opioid use and trauma. Conclusion: Analgesic outcomes should be an integral part of assessment of proficiency in regional anesthesia techniques. Evaluating outcomes of procedures throughout training will longitudinally assess technical expertise.

The role of morphine-6-glucuronide (M6G) in pain control

Morphine-6beta-D-glucuronide (M6G) is an analgesically active metabolite of morphine, accounting for approximate to10% of the morphine dose when administered by systemic routes to humans. Although M6G is more hydrophilic than morphine, it crosses the blood-brain barrier, albeit relatively slowly. For this reason, it is generally thought that, after chronic dosing, M6G contributes significantly to the analgesic effects of systemically administered morphine. Owing to its polar nature, M6G is cleared from the systemic circulation primarily via renal elimination. As M6G accumulates in patients with renal impairment, there is an increased risk of M6G-induced respiratory depression in renal failure patients who are being dosed chronically with systemic morphine. Consistent with its analgesic and respiratory depressant properties, M6G binds to the p-opioid receptor in a naloxone-reversible manner. Although the affinity of M6G for the mu-opioid receptor is similar to or slightly less than that of morphine, preclinical studies in rodents show that M6G is one to two orders of magnitude more potent than morphine when administered by central routes. This major discrepancy between the markedly higher intrinsic antinociceptive potency of M6G relative to morphine, despite their similar p-opioid receptor binding affinities, is difficult to reconcile. It has been proposed that M6G mediates its pain-relieving effects through a novel 'M6G opioid receptor', while others have argued that M6G may have higher efficacy than morphine for transduction of intracellular events. When administered by parenteral routes to rodents, M6G's antinociceptive potency is no more than twofold higher than morphine. In humans, the analgesic efficacy and respiratory depressant potency of M6G relative to morphine have been assessed in a number of short-term studies involving the intrathecal or intravenous routes of administration. For example, in hip replacement patients, intrathecal M6G provided excellent postoperative analgesia but the occurrence of late respiratory depression in 10% of these patients raised serious concern about safety. In postoperative patients, intravenous M6G administered by means of patient-controlled analgesia (PCA), or bolus plus PCA, produced no analgesia in one study and limited analgesia in another. Similarly, there was a lack of significant analgesia in healthy volunteers who received intravenous M6G for the alleviation of experimental pain (carbon dioxide applied to the nasal mucosa). In contrast, satisfactory analgesia was produced by bolus doses of intravenous M6G administered to patients with cancer pain, and to healthy volunteers with experimentally-induced ischaemic, electrical or thermal (ice water) pain. Studies to date in healthy volunteers suggest that intravenous M6G may be a less potent respiratory depressant and have a lower propensity for producing nausea and vomiting than morphine. However, it is unclear whether equi-analgesic doses of M6G and morphine were compared. Clearly, more extensive short-term trials, together with studies involving chronic M6G administration, are necessary before the potential clinical utility of M6G as an analgesic drug in its own right can be determined.

Neck flexor muscle fatigue is side specific in patients with unilateral neck pain

Despite the evidence of greater fatigability of the cervical flexor muscles in neck pain patients, the effect of unilaterality of neck pain on muscle fatigue has not been investigated. This study compared myoelectric manifestations of sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue between the painful and non-painful sides in patients with chronic unilateral neck pain. Myoelectric signals were recorded from the sternal head of SCM and the AS muscles bilaterally during sub-maximal isometric cervical flexion contractions at 25% and 50% of the maximum voluntary contraction (MVC). The time course of the mean power frequency, average rectified value and conduction velocity of the electromyographic signals were calculated to quantify myoelectric manifestations of muscle fatigue. Results revealed greater estimates of the initial value and slope of the mean frequency for both the SCM and AS muscles on the side of the patient's neck pain at 25% and 50% of MVC. These results indicate greater myoelectric manifestations of muscle fatigue of the superficial cervical flexor muscles ipsilateral to the side of pain. This suggests a specificity of the effect of pain on muscle function and hence the need for specificity of therapeutic exercise in the management of neck pain patients. (C) 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Hip strategy for balance control in quiet standing is reduced in people with low back pain

Study Design. Quiet stance on supporting bases with different lengths and with different visual inputs were tested in 24 study participants with chronic low back pain (LBP) and 24 matched control subjects. Objectives. To evaluate postural adjustment strategies and visual dependence associated with LBP. Summary of Background Data. Various studies have identified balance impairments in patients with chronic LBP, with many possible causes suggested. Recent evidence indicates that study participants with LBP have impaired trunk muscle control, which may compromise the control of trunk and hip movement during postural adjustments ( e. g., hip strategy). As balance on a short base emphasizes the utilization of the hip strategy for balance control, we hypothesized that patients with LBP might have difficulties standing on short bases. Methods. Subjects stood on either flat surface or short base with different visual inputs. A task was counted as successful if balance was maintained for 70 seconds during bilateral stance and 30 seconds during unilateral stance. The number of successful tasks, horizontal shear force, and center-of-pressure motion were evaluated. Results. The hip strategy was reduced with increased visual dependence in study participants with LBP. The failure rate was more than 4 times that of the controls in the bilateral standing task on short base with eyes closed. Analysis of center-of-pressure motion also showed that they have inability to initiate and control a hip strategy. Conclusions. The inability to control a hip strategy indicates a deficit of postural control and is hypothesized to result from altered muscle control and proprioceptive impairment.

Delayed onset of transversus abdominus in long-standing groin pain

Long-standing groin pain is a persistent problem that is commonly difficult to rehabilitate. Theoretical rationale indicates a relationship between the motor control of the pelvis and long-standing groin pain; however, this link has not been investigated. Purpose: The current experiment aimed to evaluate motor control of the abdominal muscles in a group of Australian football players with and without long-standing groin pain. Methods: Ten participants with long-standing groin pain and 12 asymptomatic controls were recruited for the study. Participants were elite or subelite Australian football players. Fine-wire and surface electromyography electrodes were used to record the activity of the selected abdominal and leg muscles during a visual choice reaction-time task (active straight leg raising). Results: When the asymptomatic controls completed the active straight leg raise (ASLR) task, the transversus abdominus contracted in a feed-forward manner. However, when individuals with long-standing groin pain completed the ASLR task, the onset of transversus abdominus was delayed (P < 0.05) compared with the control group. There were no differences between groups for the onset of activity of internal oblique, external oblique, and rectus abdominus (all P > 0.05). Conclusions: The finding that the onset of transversus abdominus is delayed in individuals with long-standing groin pain is important, as it demonstrates an association between long-standing groin pain and transversus abdominus activation.

Abdominal muscle recruitment during a range of voluntary exercises

Various exercises are used to retrain the abdominal muscles in the management of low back pain and other musculoskeletal disorders. However. few studies have directly investigated the activity of all the abdominal muscles or the recruitment of regions of the abdominal muscles during these manoeuvres. This study examined the activity of different regions of transversus abdominis (TrA), obliquus internus (OI) and externus abdominis (OE), and rectus abdominis (RA), and movement of lumbar spine, pelvis and abdomen during inward movement of the lower abdominal wall, abdominal bracing, pelvic tilting, and inward movement of the lower and upper abdominal wall. Inward movement of the lower abdominal wall in supine produced greater activity of TrA compared to OI. OE and RA. During posterior pelvic tilting. middle OI was most active and with abdominal bracing. OE was predominately recruited. Regions of TrA were recruited differentially and in inverse relationship between lumbopelvic motion and TrA electromyography (EMG) was found. This study indicates that inward movement of the abdominal wall in supine produces the most independent activity of TrA relative to the other abdominal muscle, recruitment varies between regions of TrA, and observation of abdominal and lumbopelvic motion may assist in evalation of exercise performance. (c) 2004 Elsevier Ltd. All rights reserved.

The relationship of adult attachment to emotion, catastrophizing, control, threshold and tolerance, in experimentally-induced pain

Although insecure attachment has been associated with a range of variables linked with problematic adjustment to chronic pain, the causal direction of these relationships remains unclear. Adult attachment style is, theoretically, developmentally antecedent to cognitions, emotions and behaviours (and might therefore be expected to contribute to maladjustment). It can also be argued, however, that the experience of chronic pain increases attachment insecurity. This project examined this issue by determining associations between adult attachment characteristics, collected prior to an acute (coldpressor) pain experience, and a range of emotional, cognitive, pain tolerance, intensity and threshold variables collected during and after the coldpressor task. A convenience sample of 58 participants with no history of chronic pain was recruited. Results demonstrated that attachment anxiety was associated with lower pain thresholds; more stress, depression, and catastrophizing; diminished perceptions of control over pain; and diminished ability to decrease pain. Conversely, secure attachment was linked with lower levels of depression and catastrophizing, and more control over pain. Of particular interest were findings that attachment style moderated the effects of pain intensity on the tendency to catastrophize, such that insecurely attached individuals were more likely to catastrophize when reporting high pain intensity. This is the first study to link attachment with perceptions of pain in a pain-free sample. These findings cast anxious attachment as a vulnerability factor for chronic pain following acute episodes of pain, while secure attachment may provide more resilience. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Effect of experimentally induced low back pain on postural sway with breathing

Although breathing perturbs balance, in healthy individuals little sway is detected in ground reaction forces because small movements of the spine and lower limbs compensate for the postural disturbance. When people have chronic low back pain (LBP), sway at the ground is increased, possibly as a result of reduced compensatory motion of the trunk. The aim of this study was to determine whether postural compensation for breathing is reduced during experimentally induced pain. Subjects stood on a force plate with eyes open, eyes closed, and while breathing with hypercapnoea before and after injection of hypertonic saline into the right lumbar longissimus muscle to induce LBP. Motion of the lumbar spine, pelvis, and lower limbs was measured with four inclinometers fixed over bony landmarks. During experimental pain, motion of the trunk in association with breathing was reduced. However, despite this reduction in motion, there was no increase in postural sway with breathing. These data suggest that increased body sway with breathing in people with chronic LBP is not simply because of reduced trunk movement, but instead, indicates changes in coordination by the central nervous system that are not replicated by experimental nociceptor stimulation.