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Improving effects of DX-9386, a traditional Chinese medicinal prescription, on thymectomy-induced impairment of learning behaviors in mice.

The subject mice were thymectomized 4 weeks after birth. Ten months after the thymectomy, learning behaviors in passive and active avoidance performances and a spatial memory task, the contents of brain monoamines and brain choline acetyltransferase (ChAT) activity, as well as the immune response were evaluated. DX-9386, a traditional Chinese medicinal prescription consisting of ginseng, polygala, acorus and hoelen, was prepared in CE-2 mouse food (1%, w/w) and given to the thymectomized mice after the operation until all the experiments were finished. DX-9386 treatment significantly ameliorated the learning and memory ability impaired by thymectomy in passive avoidance performances and in a spatial memory task, and the mice tended to improve in the active avoidance performance of a lever press test. However, DX-9386 treatment did not improve the thymectomy-reduced immune response. The contents of hypothalamic norepinephrine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and hypothalamic ChAT activity were significantly increased in thymectomized mice, and DX-9386 restored them to the control levels. These results suggested that DX-9386 mainly affected the cognitive process of the central nervous system to ameliorate the learning and memory deficit induced by thymectomy.

Acetylcholinesterase↗

A new technique for performing total thymectomy on rabbits.

Sixty-one Japanese white rabbits underwent total thymectomies. Eight of the animals died of intraoperative hemorrhage or respiratory failure, and twelve died of postoperative hypovolemia, dehydration, malnutrition or wound infections. Forty-one rabbits survived and were used as a total thymectomy model. The whole procedure of our technique is described in detail so that even those with no experience of performing thymectomies can follow it. Some tactics especially how to deal with the thymic vessels and the pleurae, are key points. Our technique permits safe and perfect total thymectomies to be carried out on rabbits.

Animals↗

How does neonatal thymectomy affect the immune system?

BACKGROUND: The aim of this study was to determine the effects of neonatal thymectomy on the immune system in later life. METHODS AND RESULTS: Immune system tests were performed in 26 children at 1 year of age. Thirteen of them had been operated for transposition of the great arteries and had thymectomy in the same operation in the neonatal period. Thirteen control subjects were normal. Immune system tests including white blood cell count, lymphocyte count, T and B cells subgroups (CD2, CD4, CD5, CD7, CD8, CD16, CD20, CD22, CD56), mitotic reaction to phytohaemagglutinin in lymphocyte culture. White blood cell count and lymphocyte count were performed. In the statistical analysis, Mann-Whitney U and Wilcoxon rank sum W tests were used for both groups. Statistical significance was taken at a value of P < 0.05. There was no significant difference in mean white blood cell count, mean blastic transformation reaction of lymphocytes to phytohaemagglutinin, and CD7, CD4/CD8, CD20, CD22, CD56 ratios between the two groups (P > 0.05). Significant differences in mean lymphocyte number, and CD2, CD4, CD5, CD8, CD16 ratios between the two groups were defined (P < 0.05). CONCLUSIONS: In our study, it was noticed that mainly T lymphocyte subgroups were effected by neonatal thymectomy. Although no infection requiring therapy was seen in the thymectomized patients, we advise to limit total thymectomy as much as possible in neonatal heart operations.

Case-Control Studies↗

Thymectomy in human renal transplantation.

We reviewed 17 patients submitted to thymectomy via the suprasternal notch (Yoshimatsu Method I), which was performed before transplantation in 12 patients and after transplantation in 5 patients. There were no complications of thymectomy. Graft survival of our patients with thymectomy was better than that for the overall allograft survival in Japan transplant registry for the same period. Pathologic studies revealed that involution of the cortex was not observed in 5 thymuses removed from recipients who had thymectomy after transplantation even though 2 of them had received 6.4 g and 3.5 g of prednisolone for 19 months and 32 months, respectively.

Humans↗

[Thymectomy at the 2nd Surgical Clinic of the Comenius University Medical School Hospital].

Based on comparison of two groups of thymectomies (46 in 1955-1975 and 158 in 1990-1998) the authors found a marked improvement of the results of thymectomy. During the former period thymectomies had a severe postoperative course with a high lethality and low percentage of remissions. Due to the introduction of immunosuppressive treatment the lethality of thymectomies declined to almost zero and clinical and pharmacological remission resp. was recorded in 70% patients.

Adolescent↗

In vitro response of bovine thoracic duct lymphocyte to phytohaemagglutinin following adult thymectomy.

The effect of adult thymectomy on the thoracic duct lymphocyte population of yearling calves has been investigated. Four to 6 weeks after thymectomy animals showed significantly reduced thoracic duct lymphocyte concentrations when compared to non-thymectomized controls. In addition, phytohaemagglutinin responsiveness of thoracic duct lymphocytes, measured by (3H) thymidine uptake, was significantly decreased following adult thymectomy. However, this decreased response to PHA was not accompanied by a change in spontaneous isotope incorporation. It is concluded that adult thymectomy in the bovine probably leads to a reduction in the number of PHA responsive T cells in the thoracic duct lymph.

Animals↗

Anesthesia and critical care of thymectomy for myasthenia gravis.

Myasthenia gravis is an autoimmune disease resulting from the production of antibodies against the ACh receptors of the neuromuscular synapse. The thymus gland is involved in the autosensitization process, and the disease frequently is associated with thymic morphologic abnormalities. There is a consensus that all adults with generalized MG should have a thymectomy. This recommendation has been propagated by the safety of the procedure and excellent outcome. Removal of as much thymic tissue as possible (anterior mediastinal exenteration) by transsternal approach is the logical goal of thymectomy in the treatment of MG. Transcervical approach and VATS, however, are less invasive and have been used in patients who have MG unaccompanied by thymoma. Optimization of the condition of the myasthenic patients can markedly decrease the risk of surgery and improve the outcome. Two techniques have been recommended for general anesthesia in the myasthenic patient. Because of the unpredictable response to succinylcholine and the marked sensitivity to nondepolarizing muscle relaxants, some anesthesiologists avoid muscle relaxants and depend on deep inhalational anesthesia, such as halothane, isoflurane, or sevoflurane, for tracheal intubation and maintenance of anesthesia. Others, however, use a balanced technique of anesthesia that includes the use of carefully titrated muscle relaxants. The most important preoperative factor predicting the need for postoperative mechanical ventilation is the severity of bulbar involvement (Ossermann group 3 and 4), usually indicated by significant dysphagia and dysarthria associated with borderline respiratory dysfunction. Thymectomy benefits nearly 96% of patients: 46% develop complete remission, 50% are asymptomatic or improve on therapy, and 4% remain the same. The time from diagnosis to surgery is shorter than 8 months, and mild or moderate myasthenic symptoms are the main prognostic factors that predict the best outcome after thymectomy.

Anesthesia↗

Management of myasthenia gravis by extended thymectomy with anterior mediastinal dissection.

BACKGROUND: Thymectomy has continued to gain acceptance as definitive treatment for myasthenia gravis. Because of the nature of thymic embryology with scattered rests throughout the anterior mediastinum, we advocate a transsternal thymectomy with extended anterior mediastinal dissection. METHODS: A series of 48 patients with myasthenia gravis treated by thymectomy between 1979 and 1991 were reviewed. RESULTS: The mean length of duration of disease from onset to operation was 48.7 +/- 11.3 months, and the mean length of follow-up was 51.6 +/- 6.5 months. The operation was associated with a 21% morbidity rate (4% major morbidity) with no deaths. Forty-five patients (94%) have improved, requiring decreased medication. The overall drug-free remission rate was 42%. Of the 20 patients in remission, three had thymomas and four had hyperplastic glands. All of the patients who achieved drug-free remission were classified as Osserman's I or II. CONCLUSIONS: An aggressive surgical approach to myasthenia gravis can result in a high percentage of overall improvements and drug-free remissions. The best results are achieved in patients with lower-stage disease. Therefore transsternal extended thymectomy for myasthenia gravis appears to be the procedure of choice and should be advocated as soon as the diagnosis is made and the patient stabilized.

Adult↗

[310 cases of thymectomy for myasthenia gravis].

OBJECTIVE: To evaluate the clinical characteristics and long-term outcome of 310 cases of thymectomy for myasthenia Gravis. METHODS: The data of 310 patients with thymectomy were analyzed retrospectively to study the patient selection, operative techniques, perioperative management and results for myasthenia Gravis. Absolute and relative scores for clinical evaluation were used as the criteria to determine the therapeutic effects of thymectomy. RESULTS: There were no operative death and postoperative complication rates were 8.7% (27/310). The extra anatomic thymic tissue was found in up to 38.7% (120/310) patients and thymus hyperplasia occurred in 92.9% (288/310) cases. 92.6% (287/310) postoperative patients were followed up for 3 or more months; the percentage of patients being remitted, essentially remitted, significantly effective, effective and non-effective were 7.1% (22/310), 11.3% (35/310) 40.0% (124/310), 27.1% (84/310), 7.1% (22/310) respectively. The total long-term effective rate was 85.5% (265/310). The effective rate for type I, IIa, IIb, III, IV was 90.9% (20/22), 97.6% (40/41), 95.3% (162/170), 80.6% (29/36), 77.8% (14/18) respectively. CONCLUSIONS: Generalized typed and properly selected recurrent ocular-typed patients with Myasthenia Gravis undergoing extensive thymectomy would have good long-term outcomes.

Adult↗

[Role of thymectomy in the treatment of myasthenia gravis: considerations and personal cases].

The therapeutic impact of thymectomy on the clinical course of myasthenia gravis is still very controversial. In fact, while nowadays the surgical approach is widely adopted for thymomas, its role is still debatable in patients suffering from myasthenia gravis. The surgical approach of choice for total thymectomy is represented by median sternotomy. Other surgical methodologies include cervical access and partial sternotomy. All these approaches have shown excellent results in the exeresis of the thymus. More recently video-assisted thoracoscopic thymectomy has been proposed as a less invasive and similarly effective technique for the removal of this organ and the treatment of myasthenia gravis. Aim of the present study is to report Author's experience with thymectomy, emphasizing the data available in the international literature on the surgical mortality, complications and aesthetical results of the different surgical accesses.

Adult↗

[Anesthetic management for video-assisted extended thymectomy of patients with myasthenia gravis].

BACKGROUND: Thymectomy is one of therapeutic modalities for patients with myasthenia gravis. Since 1998, we have performed video-assisted extended thymectomy, which is much less invasive than traditional method. However, its optimal perioperative management has not been established. METHODS: From April 1998 to December 2003, 40 patients with myasthenia gravis underwent video-assisted extended thymectomy in our hospital. Anesthesia was maintained with propofol, sevoflurane and epidural anesthesia. No muscle relaxant was used. Operations were performed in supine position and required differential lung ventilation of both sides in turn for manipulation. A central venous catheter was inserted in the femoral vein to prepare for unexpected bleeding or other hemodynamic changes. RESULTS: Seven patients presented hypoxemia under differential lung ventilation and needed bilateral lung ventilation or addition of CPAP to nondependent lung. Unexpected bleeding from the left innominate vein occurred in two patients and required median sternotomy. Severe hypotension caused by compression of the heart during operation was observed in twenty-one patients. Extubation in the operating room was successful in all patients except one with severe bulbar paralysis before preoperative period. CONCLUSIONS: It is important to examine both surgical techniques of video-assisted surgery and physiological features of myasthenia gravis for anesthetic management of video-assisted extended thymectomy.

Adult↗

Evaluation of electrophysiological response to thymectomy in patients with myasthenia gravis.

Clinical response to thymectomy in patients with myasthenia gravis varies in terms of timing and degree of improvement. Electrophysiological test is a reasonably reliable and objective way to evaluate neuromuscular transmission in these patients. The purpose of this study was to evaluate the electrophysiological response before and after thymectomy by repetitive nerve stimulation test in order to estimate the timing of initial improvement, progress and degree of improvement after thymectomy. According to electrophysiological findings, it appeared that neuromuscular transmission in these patients might have begun to improve even as early as one week after thymectomy and steadily improved by the end of one year of the study corresponding to clinical improvement.

Action Potentials↗

[Video-assisted thoracoscopic extended thymectomy for myasthenia gravis: analysis of 107 cases].

OBJECTIVE: To evaluate the results of video-assisted thoracoscopic extended thymectomy for myasthenia gravis. METHODS: We retrospectively reviewed data from 107 patients received thoracoscopic extended thymectomy from June 1995 to June 2004. All patients had confirmed diagnosis of myasthenia gravis by clinical manifestation and electromyogram. Thoracoscopic extended thymectomy as well as dissection of all fatty tissue anterior to the pericardium was performed. RESULTS: During a follow-up of 1-98 months, symptom was significantly improved in 83% of patients, including 34 patients experienced complete remission. There was no postoperative mortality. CONCLUSION: Favorable results of video-assisted thoracoscopic extended thymectomy can be achieved in patients with myasthenia gravis. The technique is safe and minimally invasive.

Adolescent↗

[Thoracoscopic thymectomy in the treatment of myasthenia gravis].

A series of 151 thoracoscopic thymectomy performed in the Department of General Surgery and Liver Transplantation of the Fundeni Clinical Institute between April 1999 and April 2004 is analyzed. These were 89.34% from all the thymectomies performed in our department in this period. Thoracoscopic thymectomies were performed on 131 female patients (86.75%) and 20 male patients (23.25%), aged between 8 and 60 years. All patients were previously treated in the Neurological Department of the Fundeni Clinical Institute for at least 3 months. The thoracoscopic thymectomy was indicated for: myasthenia gravis without thymic neoplasia (141 cases), stage I Masaoka thymoma (8 cases), remnant postoperative thymic tissue (3 cases). We have used a left thoracoscopic approach in 73 cases and a right thoracoscopic approach in 76 cases. In 2 cases a mixed cervical and thoracoscopic approach was needed.. No mortality and morbidity 6.62% (10 cases). From this 151 patients 100 have been constantly followed for more then one year. From the other 51, 32 are in the first postoperative year, and the other 19, 12.58% have been lost in surveillance. The one year evaluation regarding the Research Standards of Myasthenia Gravis Task Force Foundation shows: improvement--90% (complete stable remission--14%; pharmacological remission--20%; minimal manifestation--56%), unchanged--8%, worsened--2%. Our results with a complete stable remission of 14% at the end of the first year and 50% at 5 years are at least comparable with literature results with other open or thoracoscopic approaches.

Adolescent↗

[Video-assisted, extended thymectomy for the treatment of myasthenia gravis. Our early experiences].

INTRODUCTION: Extended thymectomy is the key-point of the surgical treatment of the myasthenia gravis (MG), when the thymus with the surrounding fatty tissue on the neck and in the mediastinum is removed. In this study we present a new surgical technique introduced into our practice in November 2004, and with that the thymectomy is performed with video-thoracoscopic method, without sternotomy. PATIENTS AND METHODS: Since November 2004, 6 patients (5 females and 1 male) were operated on for MG. Mean age was 26.2 years (17-41). Symptoms of MG was only ocular in 1 case (Stage I) and mild generalized in 5 cases (Stage II/B). The average preoperative period of the MG was 4 months (1-12). At the beginning of the surgery, the superior poles of the thymus were exposed and the fatty tissue surrounding the thymus in front of the trachea was removed. After that, the sternum was elevated with sternal retractors inserted under the sternum in the cervical and in a subxiphoid incisions. The thymectomy with the removal of the mediastinal fatty tissue was performed with bilateral video-assisted method. RESULTS: Mean operative time was 170 (120-210) minutes. There was no conversion to sternotomy, and there were no mortality and serious morbidity. Patients were extubated in the operating room. Chest tubes were removed on the first and second postoperative days. Mean postoperative hospitalization was 6.3 (5-7) days. At the one-month follow-up, there was 1 complete remission and 5 remissions with medication. In 1 case, the pathology revealed extrathymic thymus tissue in the cervical fat. There were 3 thymus hyperplasias, 2 thymitis and 1 thymic cyst as the pathological disorders of the thymus. CONCLUSIONS: The video-assisted extended thymectomy for MG, that was introduced into our practice, is a safe surgical procedure with good results. The postoperative period is easier for the patients, and the MG was improved in each cases.

Adolescent↗

Clinical outcomes following extended thymectomy for myasthenia gravis: report of 17 cases.

PURPOSE: This retrospective study was undertaken to assess the changes in the clinical status of patients with generalized myasthenia gravis (MG) treated with extended thymectomy and to identify prognostic variables that may be of significance in optimizing patient selection. PATIENTS AND METHODS: We reviewed the clinical outcomes of 17 patients who underwent extended thymectomy for MG. Main factors influencing the outcome are changes in clinical stage and medication requirement before and after thymectomy, age, sex, duration of disease, stage of disease, antibody status, histological characteristics of the thymus, and duration of follow-up. RESULTS: There was remission in 4 patients (23.5%), improvement in 9 patients (53%), and no change in 4 patients (23.5%). Patients in Osserman stage IIB and with a higher rate of decrease in acetylcholine receptor (AchR) antibody ratio showed a greater degree of postoperative improvement. Age of the patient, sex, presence or absence of thymoma, and time elapsed between diagnosis and operations were not found to be significant prognostic factors. CONCLUSION: The present study demonstrated that extended thymectomy for MG is an effective therapy with no great morbidity or mortality. Patients in preoperative stage IIB and with higher rate of change in the AchR antibody titer showed the greatest degree of postoperative improvement.

Adolescent↗

[Effect of thymectomy in treatment of myasthenia gravis: analysis of 67 cases].

OBJECTIVE: To evaluate the clinical effects of thymectomy in treatment of myasthenia gravis: (MG). METHODS: The clinical data of 67 patients, 29 males and 38 females, aged 10.5 - 68, who underwent thymectomy were analyzed. RESULTS: According to the Monden's standard the overall effective rate of thymectomy was 71.6%. The remission rate was 32.8% (22/6), the improvement rate was 38.8% (26/67), 14 patients showed no change (20.9%), and deterioration was seen in 5 patients (7.5%). CONCLUSION: An effective method to treat MG, thymectomy should be performed on most of the MG patients early and actively.

Adolescent↗

[The effect of thymectomy in patients with myasthenia gravis without thymoma; a statistical analysis].

In order to determine the effect of thymectomy on the prognosis of patients with myasthenia gravis, an analytical-descriptive study was carried out in the Neurological Clinic of the Groningen University Hospital and the Mathematical Institute of Groningen University. In 183 patients with generalized myasthenia gravis without thymoma, with onset between 9 and 46 years of age, the severity of the disease was scored by one neurologist at fixed times (0.5, 1, 2, 3, etcetera up to 15 years) after onset. Thymectomy was performed in 144 patients at different times (0.5, 1, 2, 3, etcetera up to 7 years) after onset. Logistic regression analysis was carried out with, as the criterion for marked improvement, a decrease of the disease score by 50%. Using this criterion, age, sex, duration of the disease and severity of the disease prior to operation played no distinct parts as prognostic factors. At different periods after the onset of the disease, groups of patients operated or not (yet) operated were compared. Patients subjected to thymectomy within 5 years after onset of myasthenia gravis had a better probability of halving of the severity score than patients not subjected to operation. These data render it possible in the individual patient to make an adequate estimate of the probability of marked improvement if thymectomy is performed or postponed.

Adolescent↗