Rouzbeh Motiei-Langroudi

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1–7.5 mg/kg) significantly increases the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal administration of agmatine (1–40 mg/kg) alone does not induce either CPP or conditioned place aversion, while combination of agmatine and subeffective doses of morphine leads to potent rewarding effects. Lower doses of morphine (0.1, 0.05, and 0.01 mg/kg) are able to induce CPP in mice pretreated with agmatine 1, 5, and 10 mg/kg, respectively. Concomitant intraperitoneal administration of UK 14 304 (0.5 mg/kg), a highly selective α2-agonist, with per se noneffective dose of morphine (0.5 mg/kg) and also its combination with noneffective doses of agmatine (1 mg/kg) plus morphine (0.05 mg/kg) produces significant CPP. UK 14 304 (0.05, 0.5 mg/kg) alone, or in combination with agmatine (1, 5 mg/kg) have had no effect. We have further investigated the possible involvement of the α2-adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective α2-antagonists, yohimbine (0.005 mg/kg) and RX821002 (0.1, 0.5 mg/kg), block the CPP induced by concomitant administration of agmatine (5 mg/kg) and morphine (0.05 mg/kg). Yohimbine (0.001–0.05 mg/kg) or RX821002 (0.05–0.5 mg/kg) alone or in combination with morphine (0.05 mg/kg) or agmatine (5 mg/kg) fail to show any significant place preference or aversion. Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve α2-adrenergic receptors.

Transsphenoidal Surgery for Growth Hormone–Secreting Pituitary Adenomas in 130 Patients

OBJECTIVE Transsphenoid surgery is the treatment of choice for growth hormone (GH)-producing pituitary adenomas. The measures that may predict postoperative remission need to be elucidated. METHODS Transsphenoid surgery was performed in 163 patients by a single neurosurgeon from 1992 until 2010. Thirty-three patients were lost to follow-up, and the results of the remaining 130 are presented here. RESULTS A total of 81.5% of patients obtained a first postoperative day GH level less than 5 μg/L, whereas 60.5% achieved a value less than 2.5 μg/L. A total of 56.9% had achieved both a GH less than 2.5 μg/L and normal insulin-like growth factor I (IGF-I) on delayed follow-up and could be regarded as in remission. Duration of symptoms before surgery, age, preoperative GH, and IGF-I levels did not significantly influence a patients remission. Analysis showed that cavernous sinus extension and larger tumor size were associated with decreased remission rate, whereas sellar floor invasion or suprasellar extension did not significantly influence remission. CONCLUSION The results of our study show that transsphenoid surgery is an optimal treatment modality for GH-secreting pituitary adenoma. Suprasellar or sellar floor invasion, and preoperative GH or IGF-I do not necessarily predict poor outcomes. Large tumor size and cavernous sinus extension contribute to greater recurrence rates.

Use of Platelet Function Testing Before Pipeline Embolization Device Placement: A Multicenter Cohort Study

Background and Purpose— Thromboembolic complications constitute a significant source of morbidity after neurointerventional procedures. Flow diversion using the pipeline embolization device for the treatment of intracranial aneurysms necessitates the use of dual antiplatelet therapy to reduce this risk. The use of platelet function testing before pipeline embolization device placement remains controversial. Methods— A retrospective review of prospectively maintained databases at 3 academic institutions was performed from the years 2009 to 2016 to identify patients with intracranial aneurysms treated with pipeline embolization device placement. Clinical and radiographic data were analyzed with emphasis on thromboembolic complications and clopidogrel responsiveness. Results— A total of 402 patients underwent 414 pipeline embolization device procedures for the treatment of 465 intracranial aneurysms. Thromboembolic complications were encountered in 9.2% of procedures and were symptomatic in 5.6%. Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications compared with clopidogrel responders (17.4% versus 5.6%). This risk was significantly lower in nonresponders who were switched to ticagrelor when compared with patients who remained on clopidogrel (2.7% versus 24.4%). In patients who remained on clopidogrel, the rate of thromboembolic complications was significantly lower in those who received a clopidogrel boost within 24 hours pre-procedure when compared with those who did not (9.8% versus 51.9%). There was no significant difference in the rate of hemorrhagic complications between groups. Conclusions— Clopidogrel nonresponders experienced a significantly higher rate of thromboembolic complications when compared with clopidogrel responders. However, this risk seems to be mitigated in nonresponders who were switched to ticagrelor or received a clopidogrel boost within 24 hours pre-procedure.

Use of Immunohistochemistry Techniques in Patients Exposed to Sulphur Mustard Gas

We performed a pathologic study with further using an immunohistochemical technique (using anti-p63 and anti-CK5) on tissues obtained by open lung biopsy from 18 patients with previous exposure to sulphur mustard (SM) as case group and 8 unexposed patients (control group). The most frequent pathologic diagnosis was constrictive bronchiolitis (44.4%), followed by respiratory (22.2%) and chronic cellular bronchiolitis (16.7%) in the case group, and hypersensitivity bronchiolitis (50%) in the control group. The pathologic diagnoses were significantly different in the case and control groups (P = 0.042). In slides stained by anti-p63 and anti-CK5, the percent of stained cells and the mean number of epithelial cells were lower in the case group in comparison to the control group. This difference was significant for the mean number of cells stained by anti-CK5 (P = 0.042). Furthermore, there was a significant correlation between pathologic diagnosis and total number of cells and mean number of cells stained with anti-p63 and anti-CK5 (P  value = 0.002, <0.001, 0.044). These results suggest that constrictive bronchiolitis may be the major pathologic consequence of exposure to SM. Moreover, decrease of p63 in respiratory tissues affected by SM may suggest the lack of regenerative capacity in these patients.

Helium:oxygen versus air:oxygen noninvasive positive-pressure ventilation in patients exposed to sulfur mustard

Exposure to sulfur mustard (SM) causes a variety of respiratory symptoms, such as chronic bronchitis and constrictive bronchiolitis. This study assessed the effectiveness of noninvasive positive-pressure ventilation, adjunct with 79:21 helium:oxygen instead of 79:21 air:oxygen, in 24 patients with a previous exposure to SM presenting with acute respiratory failure. Both air:oxygen and helium:oxygen significantly decreased systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse rate, respiratory rate, dyspnea, and increased oxygen saturation (P values: .007, .029, .002, <.001, <.001, <.001, and .002 for air:oxygen, respectively, and <.001, .020, .001, <.001, <.001, <.001, and .002, for helium:oxygen, respectively). Moreover, helium:oxygen more potently improved systolic pressure, mean arterial pressure, pulse rate, respiratory rate, and dyspnea (P values: .012, .048, <.001, <.001, and .012, respectively). The results of our study support the benefit of using helium:oxygen adjunct with noninvasive positive-pressure ventilation in patients exposed to SM with acute respiratory decompensation.

Assessment of pedicle screw placement accuracy in thoracolumbosacral spine using freehand technique aided by lateral fluoroscopy: results of postoperative computed tomography in 114 patients.

BACKGROUND CONTEXT Pedicle screw fixation is currently widely used in spine surgery for various pathologies. Increasing screw placement accuracy would improve the outcomes. PURPOSE To determine the accuracy rate of screw placement in a group of patients who underwent pedicle screw fixation with conventional techniques. STUDY DESIGN A case series. PATIENT SAMPLE It includes patients undergoing posterior spinal fixation with pedicle screw insertion. Outcome measures include the accuracy of screw placement in pedicles defined by postoperative computed tomography (CT). METHODS After surgery, an axial thin-cut CT scan was performed in all patients. Screw position was classified as correct when the screw was completely surrounded by the pedicle cortex and incorrect when any part of the screw was outside the pedicle boundaries. RESULTS Seven hundred seventy screws were inserted at vertebral levels T7-S1 of 114 patients between March 2012 and December 2012. There were three wound infections and one death. Eighteen screws were diagnosed as having an incorrect position (2.3%). The highest accuracy was observed in levels L4 and L5 (0.8% inaccuracy rate for each), whereas the highest inaccuracy rate was observed in T9. The mean inaccuracy rate was 10.5% for levels T7-T9, 3.5% for levels T10-L2, and 0.9% for levels L3-S1. The differences were statistically significant. Only one screw (5%) needed revision. CONCLUSIONS The results of our study show that conventional methods for pedicle screw placement remain safe and accurate, with best results obtained in the lumbosacral spine, followed by the thoracolumbar junction. Nonetheless, results are less accurate in the midthoracic spine.

Furosemide Inhalation in Dyspnea of Mustard Gas-Exposed Patients: A Triple-Blind Randomized Study

Dyspnea is the hallmark symptom of some respiratory diseases such as chronic obstructive pulmonary disease and bronchiolitis and is a major reason for which these patients seek medical attention. We performed a randomized triple-blind controlled crossover clinical trial in which we compared the efficacy of inhaled furosemide (4 ml equal to 40 mg in 10 min) with placebo (4 ml of 0.9% saline solution) in 41 mustard gas-exposed patients. Dyspnea index, visual analog scale (VAS), and pulmonary function test results were obtained before and 4 h after treatments. Results showed that both furosemide and placebo significantly decreased VAS and dyspnea index and increased FEV1, FVC, and FEV1/FVC, while there was no difference between the two drugs in these effects (p values.23, .61, .81, .36, and.27, respectively). Our results failed to address the previously reported effects of inhaled furosemide on dyspnea. In fact, we suggest that patients with a previous exposure to sulfur mustard, in which chronic bronchitis and bronchiolitis are the most suggested underlying mechanisms, may not benefit from furosemide to alleviate their dyspnea.

Kinesthetic memory in distance reproduction task: importance of initial hand position information.

The role of the initial hand position in planning and implementation of a goal-directed movement is a matter of debate. We designed a non-visually guided repetitive reaching movement task to investigate the role of proprioceptive information of the initial or end hand position in implementation of kinesthetic memory. The experimental design consisted four experiments. Each experiment consisted two phases: the training phase and the test phase. In the training phase the subjects were asked to learn and memorize the distance between start and end points by moving their hands ten times between them. In the test phase, the end point was removed, and starting from the same initial position, the subjects were asked to reproduce the memorized distance. In all experiments, varied conditions called “mask phase” preceded the test phase: a 5-s delay in experiment 1, shifting both initial and end points while keeping the distance constant in experiment 2, shifting only the end point, while keeping the initial point constant in experiment 3 and shifting only the initial point and keeping the end point constant in experiment 4. In comparison to experiment 1 (which was considered as the control group), no significant error in distance reproduction occurred in experiment 3, while experiments 2 and 4 showed significant error. These findings mean that although the distance information was available during the mask phase of experiment 2, subjects could not efficiently use this information to reproduce the distance. The other two experiments suggest that this error was caused by changing the initial hand position and not the end point. We conclude that in a kinesthetic-guided distance reproduction task, the initial hand position is more important for implementation of distance memory rather than the end point.

Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion

Background and Purpose— Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement. Methods— A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis. Results— Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis. Conclusions— Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke.

Predictors of Incomplete Occlusion following Pipeline Embolization of Intracranial Aneurysms: Is It Less Effective in Older Patients?

This was a retrospective analysis of 465 consecutive aneurysms treated with the Pipeline Embolization Device between 2009 and 2016, at 3 academic institutions in the United States. Cases with angiographic follow-up were selected to evaluate factors predictive of incomplete aneurysm occlusion at last follow-up. Older age (more than 70 years), nonsmoking status, aneurysm location within the posterior communicating artery or posterior circulation, greater aneurysm maximal diameter (>21 mm), and shorter follow-up time (<12 months) were significantly associated with incomplete aneurysm occlusion at last angiographic follow-up. BACKGROUND AND PURPOSE: Flow diversion with the Pipeline Embolization Device (PED) for the treatment of intracranial aneurysms is associated with a high rate of aneurysm occlusion. However, clinical and radiographic predictors of incomplete aneurysm occlusion are poorly defined. In this study, predictors of incomplete occlusion at last angiographic follow-up after PED treatment were assessed. MATERIALS AND METHODS: A retrospective analysis of consecutive aneurysms treated with the PED between 2009 and 2016, at 3 academic institutions in the United States, was performed. Cases with angiographic follow-up were selected to evaluate factors predictive of incomplete aneurysm occlusion at last follow-up. RESULTS: We identified 465 aneurysms treated with the PED; 380 (81.7%) aneurysms (329 procedures; median age, 58 years; female/male ratio, 4.8:1) had angiographic follow-up, and were included. Complete occlusion (100%) was achieved in 78.2% of aneurysms. Near-complete (90%–99%) and partial (<90%) occlusion were collectively achieved in 21.8% of aneurysms and defined as incomplete occlusion. Of aneurysms followed for at least 12 months (211 of 380), complete occlusion was achieved in 83.9%. Older age (older than 70 years), nonsmoking status, aneurysm location within the posterior communicating artery or posterior circulation, greater aneurysm maximal diameter (≥21 mm), and shorter follow-up time (<12 months) were significantly associated with incomplete aneurysm occlusion at last angiographic follow-up on univariable analysis. However, on multivariable logistic regression, only age, smoking status, and duration of follow-up were independently associated with occlusion status. CONCLUSIONS: Complete occlusion following PED treatment of intracranial aneurysms can be influenced by several factors related to the patient, aneurysm, and treatment. Of these factors, older age (older than 70 years) and nonsmoking status were independent predictors of incomplete occlusion. While the physiologic explanation for these findings remains unknown, identification of factors predictive of incomplete aneurysm occlusion following PED placement can assist in patient selection and counseling and might provide insight into the biologic factors affecting endothelialization.