International journal of clinical research & trials最新文献

{"title":"Application of Early Quantitative Activity Program in Accelerated Rehabilitation after Laparoscopic Hepatectomy","authors":"","doi":"10.26855/j.ijcr.20190005","DOIUrl":"https://doi.org/10.26855/j.ijcr.20190005","url":null,"abstract":"","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82805927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evaluation of Effectiveness and Outcomes of Code Blue System in a New Tertiary Care Hospital","authors":"M. Arikan, A. Ateş","doi":"10.15344/2456-8007/2019/135","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/135","url":null,"abstract":"Objective: The code blue call is used to alert the Code Blue team for patients with cardiac or respiratory arrest. The purpose of this study is to evaluate the time, the locations, and the outcomes of code blue calls. We also aimed to determine the rate of false code blue calls, and demographic data of the patients. Material and Methods: In this study, we retrospectively scanned the code blue call forms in our hospital between January 2017 and January 2018. The demographic data of the patients, the arrival time of the team, the time, the locations, and the outcomes of the calls, and the rate of false code blue calls were recorded. Results: We had 225 code blue calls in the study period. The mean arrival time of the team was 1.97±0.72 min. Most of the code blue calls were given in Palliative Care Unit (76 patients, 33.77 %), followed by Internal Medicine Services (54 patients, 24 %), and Department of Pulmonary Diseases (36 patients, 16%). The rate of false code blue calls was found to be 13.33 %. Most of the code blue calls (140 calls, 62.22 %) were during off times. A hundred patients had died (44.44 %); 88 patients had been admitted to the ICU (39.11 %); and 7 had been continued care in ward (3.11 %) by a successful intervention. Conclusion: Giving more blue code calls during off-hours and the absence of night duty doctor at the services, especially in rural hospitals like ours, emphasizes the importance of this system.","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45820551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive Brain Stimulation Paired with Standard Physical Therapy in Parkinson's Disease: A Pilot Feasibility Trial","authors":"M. Biagioni, Estelle C. Gallo, A. Son, Kush Sharma, S. Fischer, Hamzeh A. Migdadi, S. Agarwal, Tara M. Biller, Raphaela Sills, A. Feigin, A. Rocco, A. Cucca","doi":"10.15344/2456-8007/2019/134","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/134","url":null,"abstract":"Introduction: In Parkinson’s disease (PD), postural imbalance and gait disorders (PIGD) are predictors of decreased quality of life and survival. PIGD often become unresponsive to pharmacological treatments and are commonly associated with cognitive dysfunction. Physical therapy (PT) training and falls prevention education are considered effective treatments; however, improvements are generally short-lived and only partially maintained. In this population, cognitive dysfunction hampering the consolidation of new motor skills (motor learning) is one principal reason. Transcranial magnetic stimulation (TMS) is an emerging tool for neuro-rehabilitation and growing evidence supports its potential to improve motor learning. Prompted by a shared location between our TMS lab and the PT rehabilitation center, we aimed to test whether adjuvant repetitive TMS combined with PT for PIGD is a feasible neuro-rehabilitation paradigm in patients with PD. Methods: Double blind, randomized, sham-controlled, pilot trial to evaluate the feasibility of recruitment, randomization, retention, assessment procedures and implementation of adjuvant TMS paired back-toback with PT in PD patients with PIGD. Result: 41 paired sessions were completed with 100% adherence. All sessions were tolerated. There were no severe adverse events. One subject withdrew consent. Blinding of study was deemed adequate. The average time between PT and TMS administration was 13.9 (SD 7.3) minutes. After completion of the 5th enrolled subject, the study was early terminated due to relocation of the PD center away from the PT facility. Clinical outcome mean values improved at follow up; however, the small sample size prevented further analysis of efficacy. Conclusions: When the TMS device is located in the proximity of a rehabilitation setting, adjuvant TMS appears to be feasible, safe, and well tolerated in PD. The efficacy of this modality of neuro-rehabilitation and its generalizability remain to be determined.","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42639778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Risk Reduction Associated with Pharmacological Weight Loss: A Meta-Analysis.","authors":"Jesse A Kane,&nbsp;Talha Mehmood,&nbsp;Irsa Munir,&nbsp;Haroon Kamran,&nbsp;Pramod Theetha Kariyanna,&nbsp;Angelina Zhyvotovska,&nbsp;Denis Yusupov,&nbsp;Umer Javed Suleman,&nbsp;Deborah R Gustafson,&nbsp;Samy I McFarlane","doi":"10.15344/2456-8007/2019/131","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/131","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a growing pandemic that is associated with multiple cardiovascular disease (CVD) risk factors such as hypertension, diabetes, dyslipidemia and obstructive sleep apnea. With the increase in obesity rates where nearly two thirds of Americans are either obese or overweight, there has been an increase in the use of pharmacological therapy weight loss. While these therapies have shown benefit in weight reduction, the clinical impact these pharmacological agents on overall CVD outcomes has yet to be determined.</p><p><strong>Aim: </strong>We aimed to assess the effect of pharmacological agents used for weight reduction on CVD risk and all-cause mortality.</p><p><strong>Methods: </strong>We conducted a meta-analysis of peer-reviewed literature that evaluated the impact of anti-obesity drugs on cardiovascular outcomes. Key words used included: \"orlistat\", \"lorcaserin\", \"phentermine/topiramate\" or \"naltrexone/bupropion\" and \"cardiovascular outcomes\" among others. We reviewed 791 articles, only 47 studies were randomized controlled trials and only 7 studies fulfilled all the inclusion criteria including, quantitative data on cardiovascular risk factors such as, Hemoglobin A1C (A1C), changes in body mass index (BMI), blood pressure and CVD morbidity and mortality. Data was retrieved from these studies and evaluated with comprehensive meta-analysis software^® to assess pooled effects for medical management versus placebo.</p><p><strong>Results: </strong>There were 7 studies included in the final analysis, with a total of 18,598 subjects, of which 8,685 were in the intervention (INT) group and 9,913 in the control (CTRL) group. For all cause mortality, there were 45 events in the INT and 55 in the CTRL groups, suggesting no significant difference between the two groups (OR: 0.843, 95%CI: 0.571-1.244, Z: -0.860, P: 0.390). For CVD mortality, there were 17 events in the INT and 36 events in the CTRL groups suggesting a significant mortality benefit in the INT group (OR:0.496, 95% CI: 0.282-0.873, Z: -2.433, P: 0.015). There was a significant absolute reduction in A1C in the INT group (Hg: -0.238, 95%CI: -0.291 to -0.186, Z: -8.937, P< 0.001). The percentage weight reduction was significantly higher for the INT group compared to the CTRL group (Hg: -0.431, 95%CI: -0.477 to -0.385, Z: -18.472, P< 0.001) and the blood pressure reduction was higher for the INT group compared to the CTRL group. (Hg: -0.052, 95%CI: -0.101- -0.003, Z: -2.086, P: 0.037). The heterogeneity observed for our meta analysis is Q: 1.884, df: 6, P: 0.930.</p><p><strong>Conclusions: </strong>Our study demonstrated the favorable and significant effect of pharmacological weight reduction strategies on weight loss, blood pressure reduction, glycemic control (A1C reduction), and CVD mortality.While weight loss without pharmacological means has been shown to reduce CVD risk, the mechanism by which weight loss medications impact CVD risk reduction","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.15344/2456-8007/2019/131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10541015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marijuana and Cardiac Arrhythmias: A Scoping Study.","authors":"Pramod Theetha Kariyanna,&nbsp;Perry Wengrofsky,&nbsp;Apoorva Jayarangaiah,&nbsp;Syed Haseeb,&nbsp;Louis Salciccioli,&nbsp;Sudhanva Hegde,&nbsp;Jonathan D Marmur,&nbsp;Yasmin Soliman,&nbsp;Sama Al-Bayati,&nbsp;Samy I McFarlane","doi":"10.15344/2456-8007/2019/132","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/132","url":null,"abstract":"<p><p>With increasing legalization, marijuana has become the most commonly abused substance in the United States. Together with the introduction of more potent marijuana products over the years, more adverse events are being reported and clinically characterized. Delta-9-tetrahydrocannabinol (THC) is the active psychotropic component of marijuana, which acts mainly on G-protein cannabinoid receptors CB1 and CB2. Multiple isolated cases of arrhythmias associated with marijuana use have been published. In this manuscript we conduct a scoping study of a total of 27 cases of arrhythmia associated with marijuana. Most cases were reported in young males (81%) with a mean age of 28 ± 10.6 years. Atrial fibrillation (26%) and ventricular fibrillation (22%) were the most common arrhythmias reported. Brugada pattern was reported in 19% of the patients. Marijuana associated arrhythmia resulted in a high mortality rate of 11 %. While the exact mechanisms of arrhythmias associated with marijuana are not clear, several hypothesis have been introduced including the effect of marijuana on cardiac ion channels as well as its effects on the central nervous system. In this paper we discuss the possible mechanisms of marijuana induced arrhythmia citing the evidence available to-date.</p>","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9086110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrovascular Accident and Snake Envenomation: A Scoping Study.","authors":"Mohammed Al-Sadawi,&nbsp;Maliheh Mohamadpour,&nbsp;Angelina Zhyvotovska,&nbsp;Tahir Ahmad,&nbsp;Joshua Schechter,&nbsp;Yasmin Soliman,&nbsp;Samy I McFarlane","doi":"10.15344/2456-8007/2019/133","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/133","url":null,"abstract":"<p><strong>Background: </strong>Snake envenomation is associated with serious complications including infections, bleeding and, in rare occasions, thrombosis. Previous work by our group examined the association of snakebite and acute myocardial infarction. In this systematic review we aim to assess the clinical characteristics and outcomes of acute cerebrovascular accidents that are reported to be extremely rare complications of snake envenomation.</p><p><strong>Methods: </strong>We performed a literature search for reports on stroke associated with snake envenomation between Jan 1995 to Oct 2018, and summarized their characteristics.</p><p><strong>Results: </strong>Eighty-three published cases were reviewed. 66.3% of the cases were younger than 50 years of age. The mean time for the onset of the symptoms is 23.8±10.9 hours after exposure. 77.1% of the cases found to have ischemic stroke, 20.5% with intra-cranial hemorrhage and both infarction and hemorrhage in 2.4%. Mortality was reported in 16.9% with mean time between onset of the symptoms and death is 4.2 days.</p><p><strong>Conclusion: </strong>Stroke secondary to snake envenomation is a rare but serious complication. Once stroke is suspected, initiating appropriate management is crucial in reducing morbidity and mortality associated with this potentially fatal complication of snake envenomation.</p>","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9086108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diastolic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Case Controlled Studies.","authors":"Angelina Zhyvotovska,&nbsp;Denis Yusupov,&nbsp;Haroon Kamran,&nbsp;Tarik Al-Bermani,&nbsp;Rishard Abdul,&nbsp;Samir Kumar,&nbsp;Nikita Mogar,&nbsp;Angeleque Hartt,&nbsp;Louis Salciccioli,&nbsp;Samy I McFarlane","doi":"10.15344/2456-8007/2019/137","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/137","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) and left ventricular diastolic dysfunction (LVDD) are major causes of morbidity and mortality and have overlapping symptomatology including cough and dyspnea. Whether COPD is a risk factor for LVDD remains largely unclear.The objective of this meta-analysis was to determine if the prevalence of the LVDD as determined by echocardiographic parameters is increased in COPD patients.</p><p><strong>Methods: </strong>We used a time-and-language-restricted search strategy resulting in identification of 4,912 studies of which 15 studies met our apriori inclusion criteria; 4,897 were excluded, such duplicates, foreign language articles were excluded. We performed a meta-analysis of standard echo parameters on the fifteen case control studies related to diastolic dysfunction. The meta-analysis was performed using Review Manager, version 5.3 (Cochrane Collaboration).</p><p><strong>Results: </strong>A total of 15 studies with 1,403 subjects were included. There were no differences in left ventricular ejection fraction between COPD and non-COPD population. Patients with COPD had prolonged isovolumetric relaxation time (IVRT) (mean difference 20.84 [95% CI 12.21, 29.47]; P< 0.00001), lower E/A ratio (mean difference - 0.24 [95% CI -0.34, 00.14]; P < 0.00001), higher transmitral A wave peak velocity (Apv) (mean difference 11.71 [95% CI 4.80, 18.62]; P< 0.00001), higher E/e' ratio (mean difference 1.88 [95% CI 1.23, 2.53]; P< 0.00001), lower mitral E wave peak velocity (Epv) (mean difference -8.74 [95% CI -13.63, -3.85]; P< 0.0005), prolonged deceleration time (DT) (mean difference 50.24 [95% CI 15.60, 84,89]; P< 0.004), a higher right ventricular end diastolic diameter (RVEDD) (mean difference 8.02 [95% CI 3.45, 12.60]; P< 0.0006) compared to controls. COPD patients had a higher pulmonary arterial pressure (mean difference 10.52 [95% CI 3.98, 17.05]; P< 0.002). Differences in septal e' velocity (mean difference -2.69 [95% CI -6.07, 0.69]; P< 0.12) and in lateral e' velocity (mean difference -2.84 [95% CI 5.91, 0.24]; P< 0.07) trended towards significance but did not meet our cutoff for statistical significance (p < 0.05).</p><p><strong>Conclusions: </strong>Patients with COPD are more likely to have LVDD as established by echocardiographic parameters. Our findings are likely explainable, in part, by factors such as lung hyperinflation, chronic hypoxia, hypercapnia, systemic inflammation, increased arterial stiffness, subendocardial ischemia, as well as ventricular interdependence; all of which might contribute to the pathogenesis of diastolic dysfunction. Further research is needed to elucidate the pathophysiologic mechanisms of increased LVDD in the COPD population with the potential impact on developing effective therapeutic interventions for these serious disorders.</p>","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10545446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of a Transitional Care Clinic to Reduce Heart Failure Readmissions at an Urban Academic Medical Center.","authors":"Justin Lee,&nbsp;Felix Reyes,&nbsp;Minhazul Islam,&nbsp;Mafuzur Rahman,&nbsp;Miguel Ramirez,&nbsp;Jonathan Francois,&nbsp;Samy I McFarlane","doi":"10.15344/2456-8007/2019/140","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/140","url":null,"abstract":"<p><p>Heart Failure (HF) is one of the leading hospital readmission diagnoses in the United States. It is a major challenge in today's healthcare environment to reduce hospital readmissions for HF and much of the expenditure on HF is on in-hospital treatment. In the USA, risk factors for readmission with HF include being African American, low-socioeconomic status, Medicare, Medicaid, self-pay/no insurance and drug abuse. The Transitional Care Clinic (TCC) model established at our institution integrated multiple facets of chronic HF management, including early post-discharge follow-up, phone call reminders as well as clinical pharmacists and nurse practitioner's integration into the treatment team. Of 488 HF admissions to our institution from March 2015 until May 2017, mean age = 65 years (SD 13.03), 262 patients were males (53.6%) and 463 patients (94%) were Blacks. There was a total of 121 readmissions within 30 days after discharge (24.8%) and 43 readmissions 7 days after discharge (8.81%) during our study period. 159 patients (32.58%) followed up in our TCC, while 329 patients (67.41%) did not at TCC. Within 7 days post discharge, there was 3 (1.9%) Vs 40 (12.2%) readmissions for TCC and non-TCC groups respectively, P<0.01. There was 18 (11.32%) Vs 103(31.31%) readmissions within 30 days post discharge for TCC and non-TCC groups respectively P<0.01. Among high readmission risk and predominantly black population with HF, TCC resulted in significantly lower hospital readmission rate within 7 days and within 30 days of initial discharge. These data help inform policy makers regarding the effectiveness of TCC model for resource allocation and broader implementation, particularly among high risk population with the potential of cost saving and better patient outcomes.</p>","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocular Manifestations of Rheumatoid Arthritis: Implications of Recent Clinical Trials.","authors":"Manjeet S Bhamra,&nbsp;Irfan Gondal,&nbsp;Abhimanyu Amarnani,&nbsp;Saul Betesh,&nbsp;Angelina Zhyvotovska,&nbsp;Wayne Scott,&nbsp;Milena Rodriguez-Alvarez,&nbsp;Douglas R Lazzaro,&nbsp;Isabel M McFarlane","doi":"10.15344/2456-8007/2019/139","DOIUrl":"https://doi.org/10.15344/2456-8007/2019/139","url":null,"abstract":"<p><p>While rheumatoid arthritis (RA) typically presents with synovitis of the small and medium joints of the hands, ocular manifestations of the disease are generally overlooked and largely underdiagnosed. These complications usually present in longstanding RA population and occasionally represents the first manifestation of the disease and generally affect the anterior chamber of the eye, leading to keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis and anterior uveitis. In this review, we present the current understanding of the pathophysiologic mechanisms for ocular disease in RA, including the role of oxidative stress, cytokine imbalance, chronic inflammation, vascular permeability, immune complex deposition and the role of T-cells as well as the contribution of tear hyperosmolarity among other factors. We also discuss the clinical presentation and diagnosis of each of the ocular disease entities highlighting the latest strategies in the management of this serious disorders that could potentially lead to blindness and the implications of recently completed and ongoing clinical trials in the field. While RA disease control is the cornerstone in the management of RA-associated ocular manifestations, early recognition of ocular pathology with prompt referral to ophthalmology is of paramount importance in order to prevent blindness and improve the quality of life in this patient population.</p>","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cortical Substrate for Parkinsonism: A Personal Journey","authors":"G. Arbuthnott, M. G. Muñoz","doi":"10.15344/2456-8007/2018/130","DOIUrl":"https://doi.org/10.15344/2456-8007/2018/130","url":null,"abstract":"We first started thinking that cortex must be important in Parkinson’s disease when Alan R. Crossman did some experiments in rats, showing transient reductions in 6-hydroxydopamineinduced spontaneous turning behavior after cortical lesions [1]. The experiments were elegant, but the lesions were large and did not block the turning, suggesting a kind of competition rather than a causal influence of cortex in the turning behavior. Similar conclusions plagued the many attempts to decide which of the brainstem pathways were the substrate of the turning behavior that followed the destruction of dopamine cells unilaterally, for review see, Arbuthnott and Wright [2]. However, as we finished a study of the anatomy of the basal ganglia [3] we concluded that the final output from the striatum came through the output nuclei of the basal ganglia: the globus pallidus pars interna (entopeduncular nucleus in rodents) and the substantia nigra pars reticulata, to a small nucleus in the ventral thalamus (ventromedial -VMin the rat). Tracing the output from that nucleus brought us back to layer 1 of the cortex, close to where the search started in layer V [3]. This result had the basal ganglia appearing to be a loop ‘linking’ layer 5 to the superficial level of the cortex. Not a very likely scenario, nevertheless it did prepare us to look for an involvement of cortex in the consequences of dopamine destruction. Furthermore, the evidence was already there, the striatal spiny projection neurons (SPNs) that carried the first stage of the basal ganglia output, have cortical synapses on the spines [4]. When we studied the electron microscopic (EM) anatomy of the striatum without dopamine, there were obvious differences in those SPN spines [5-7]. There were fewer of them: we counted them stereologically in serial EM sections and found statistically fewer spines when the dopamine had been removed. As the theory about the differences in the two output pathways from the striatum developed, we started a long series of experiments where we identified the cells on which the spines were counted. By then, we were not alone and the final publication brought together the laboratories of Susan R. Sesack, Ariel Y. Deutch, Jim D. Surmeier, and ourselves [8]. It may be that we missed some dopamine D1 cells that were also denuded of spines [9], but the major effect was robust across all our studies. Therefore, damage to the dopamine input to the striatum, somehow spread to the cortical synapses on the spines of the SPNs. We did most of the work on rats but we also checked that the effect occurred in Parkinsonian patients. In fact, in post mortem human brain the effects were even more marked, with a 27% reduction in spine numbers compared with the 15% in the rats [10].","PeriodicalId":73437,"journal":{"name":"International journal of clinical research & trials","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44804601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}