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The parietal cell autoantigens recognized in neonatal thymectomy-induced murine gastritis are the alpha and beta subunits of the gastric proton pump [corrected].

Murine autoimmune gastritis, induced by neonatal thymectomy, bears a striking similarity in pathology to the human autoimmune disease, pernicious anemia. Autoantibodies to parietal cells are found in both murine and human diseases. Monoclonal immunoglobulin G autoantibodies, obtained from neonatally thymectomized mice, have previously been shown to recognize two groups of gastric parietal cell antigens. In the present study, it is shown that two of these monoclonal autoantibodies, designated 1H9 and 2B6, are directed against the alpha subunit and beta subunit, respectively, of the gastric hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase; proton pump). Monoclonal antibody 1H9 showed reactivity by immunoblotting with a 95-kilodalton component of dog gastric tubulovesicular membranes and with a fusion protein containing the hydrophilic domain of the alpha subunit of the H+,K(+)-ATPase. Monoclonal antibody 2B6 reacted by immunoblotting with the 60-90-kilodalton glycoprotein (beta subunit) of the tomato lectin-purified dog H+,K(+)-ATPase and with the 60-90-kilodalton autoantigen purified with human parietal cell autoantibodies. Monoclonal antibody 2B6 also reacted with the deglycosylated 35-kilodalton core protein of the tomato lectin-purified 60-90-kilodalton beta subunit and of the purified 60-90-kilodalton autoantigen. Parietal cell autoantibody-positive sera from 20 mice with experimentally induced gastritis showed reactivity predominantly with the alpha and/or beta subunit of the gastric H+,K(+)-ATPase. Therefore, it is concluded that the major molecules targeted by parietal cell autoantibodies from mice with neonatal thymectomy-induced murine autoimmune gastritis and from humans with pernicious anemia are identical.

Adenosine Triphosphatases↗

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 3. The effect of thymectomy.

The clinical condition and the serum levels of antibodies to acetylcholine receptor protein were followed in 30 patients with myasthenia gravis before and in a period varying from 2 to 4 (mean 3) yr after thymectomy. Twenty-five patients improved in the 2 yr following thymectomy. A highly significant correlation was found between the change in clinical condition and the change in antibody levels. Only 3 patients improved without a fall of antibody level. Prethymectomy antibody levels were positively correlated with the severity of the clinical condition and with the degree of thymus hypertrophy.

Adolescent↗

Response to thymectomy in Chinese patients with myasthenia gravis.

Myasthenia gravis was diagnosed in 48 patients between 1985 and 1991 in this Chinese community. Thymectomy was performed on 36 patients and the mean postoperative follow-up period was 49 months. Significant improvement was seen in 72% of the thymectomised patients, with 33% achieving complete remission. Patients with mild generalised myasthenia at presentation or those found to have thymic hyperplasia had the best prognosis. Patients with more severe symptoms or those with an underlying thymoma also responded favourably. Only patients with ocular myasthenia or those with a normal or atrophic thymus gland had no more than an even chance of gaining significant improvement. Although previous reports suggested a high prevalence of ocular myasthenia and of thymoma among Chinese myasthenic patients, the present study has found no evidence that they respond differently to thymectomy than their Western counterparts.

Adolescent↗

Effects of thymectomy on reproductive function and behavior.

The effects of thymectomy in perinatal Long-Evans rat pups on their reproductive function in early adulthood were examined. Thymectomized females had decreased lordotic responsivity to estrogen, while thymectomized males exhibited differences in mount latency or postejaculatory interval; these results suggest a possible influence of the thymus on the normal development of the neural substrates of sexual behavior. Gonadal histology appeared unperturbed in rats of either sex. No statistical abnormalities in luteinizing hormone or testosterone levels were seen in male animals. Likewise, no disturbances were observed in the ability of females to exhibit normal positive feedback after estrogen and progesterone administration; negative feedback after unilateral ovariectomy (as judged by ovarian compensatory hypertrophy) was also normal. The timing of puberty was not statistically delayed in females, even though slowed growth rates were observed. A heightened surgical stress response, as judged by progesterone levels in experimental females, suggests that perinatal thymectomy may possibly alter the sensitivity of adults to stress.

Animals↗

Depletion of helper/inducer T cells after thymectomy in myasthenic patients.

Using monoclonal anti-T-cell antibodies, we have studied peripheral blood T-cell subsets in 53 patients with myasthenia gravis before and after thymectomy (Tx). Before Tx, the mean OKT4/OKT8 ratio was higher in patients than in controls. Furthermore patients showed a high number of cells reacting simultaneously with the OKT4 and OKT8 antibodies. Shortly after surgery, the helper/suppressor ratio was increased in most of the patients, and the doubly reactive subset decreased to normal levels. However, 6 to 12 months after Tx the OKT4/OKT8 ratio was significantly decreased, particularly in patients showing clinical improvement. The percentage of total T cells was slightly but significantly reduced. A group of 14 patients studied more than 2 years after Tx presented very low OKT4/OKT8 ratios. Thymectomy in MG appears to lead to a gradual decrease of the T-helper subset which could contribute to its favorable effect on the course of the disease.

Adult↗

Effect of neonatal thymectomy and antilymphocyte globulin on non-specific mitogen stimulation in Holstein-Friesian calves.

Nine of seventeen neonatal Holstein-Friesian calves were thymectomized, treated with antilymphocyte globulin, and monitored for immunologic functional ability for 4 to 6 months. The thymus weights for 4 to 10-day-old calves and 4 to 6-month-old calves indicated a continued increase in total weight. This indicated significant thymic involution had not occurred at 4 to 6 months. Following thymectomy a wasting syndrome was not observed although an increased incidence of a lowly virulent virus infection did occur. A significant decrease in circulating lymphocytes was observed. Peripheral blood lymphocytes were stimulated in vitro by non-specific mitogens, phytohemagglutinin, bacterial lipopolysaccharide and pokeweed mitogen using the whole blood culture method. Observations included a greater response to phytohemagglutinin and pokeweed mitogen in summer months and variable age related response to all mitogens. Lipopolysaccharide stimulation results were inconclusive. It was concluded that neonatal thymectomy was not a satisfactory experimental procedure for the production of selective immunosuppression in the bovine species.

Animals↗

HLA type is not indicative for the effect of thymectomy in myasthenia gravis.

The frequency of HLA types in a selected group of 40 patients with myasthenia gravis in relation to the effect of thymectomy and also to gender, and thymus histology was studied. As generally described we found a significant increase in the frequency of HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 in the total group. There were no further differences between subgroups of patients, which demonstrates that HLA type is not indicative for the effect of thymectomy in myasthenia gravis.

Adult↗

[Results of systematic subtotal parathyroidectomy with thymectomy for tertiary hyperparathyroidism after renal transplantation - 70 patients].

BACKGROUND: Due to the relatively small number of patients involved, there is currently no consensus on what operation should be performed in patients with tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective analysis of the 70 patients with tertiary hyperparathyroidism who all underwent subtotal parathyroidectomy with transcervical thymectomy in the same institution between 1978 and 2003. RESULTS: The delay between transplantation and parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients. Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21 ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26 patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients (27%)]. One patient was successfully reoperated for persistent tertiary hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up. Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%) without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach permits not only to cure the majority of patients with tertiary hyperparathyroidism but also to avoid recurrence when the renal function declines. When medical management has failed, we recommend systematic subtotal parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism and this should usually be performed during the second year after transplantation.

Adult↗

Experience with the "da Vinci" robotic system for thymectomy in patients with myasthenia gravis: report of 33 cases.

BACKGROUND: Our initial experience in applying robotic-assisted technologies for the treatment of myasthenia gravis (MG) in patients without thymoma is reported. METHODS: from April 2002 to October 2004, 33 patients (24 females and 9 males; mean age, 41 years), with clinical nonthymomatous myasthenia gravis, underwent robotic thoracoscopic thymectomy using the "da Vinci" (Intuitive Surgical, Inc, Mountain View, CA) system and adopting a 3 port, left-sided approach. RESULTS: Mean operative time was 120 minutes. No intraoperative complications or surgical mortality is reported and postoperative complications occurred in two patients (6%). Mean hospital stay was 2.6 days (range, 2-14 days). Histologic analysis of surgical specimens revealed 23 hyperplasia, 4 normal thymus, 4 atrophy, and 2 thymomas; in 12 patients (36.3%) ectopic thymic tissue was found. Follow-up evaluation of the first 24 patients (mean, 23.8 months; range, 12-31 months) showed that 4 patients (16.7%) had complete remission and 18 (75%) had significant clinical improvement for a global benefit rate of 91.7%. CONCLUSIONS: In patients with MG, robot-assisted thymectomy can be performed safely and efficiently. The improved visualization and dexterity of this instrument and its advanced technology may facilitate the minimally invasive approach to the thymus. We prefer to use the left-sided approach because it provides an enhanced visualization of the aortic window and it reduces the probability of phrenic nerves injury. A longer follow-up is necessary to verify long-term clinical results.

Adolescent↗

Thoracoscopic thymectomy mid-term results.

BACKGROUND: Results of thymectomy in patients with myasthenia gravis need to be reported in a standardized way to allow accurate comparison. METHODS: A retrospective study was conducted of 107 patients with myasthenia gravis without thymoma. Patients were followed-up for more than 12 months after thoracoscopic thymectomy and analyzed according to Myasthenia Gravis Foundation of America Recommendations for Clinical Research Standards. RESULTS: The study population was aged 8 to 60 years old and included 15 men (14%) and 92 women (86%). A right-side approach was used in 36 patients, and the remaining 71 patients had a left-side approach. Mortality was 0% and morbidity was 9.34%. The mean operative time was 90 +/- 45 minutes. The histologic diagnosis of the resected thymus was hyperplasia (78.5%), atrophy (15%), and normal status (6.5%). The mean length of hospitalization was 2.3 days (range, 2 to 6 days). The mean follow-up was 36.4 months (range, 12 to 74 months). The rate of complete stable remission was 59.5% by the end of postoperative year 6. An earlier onset age and early operation were significantly associated with complete stable remission and pharmacologic remission. A comparison of right side versus left side approach showed similarities in mean operative time, mean length of hospitalization, histopathologic results, and remission rates. CONCLUSIONS: Outcomes of the thoracoscopic approach in myasthenia gravis without thymoma were similar to those provided by open surgery, with the acknowledged benefits of minimally invasive surgery and good patient acceptance.

Adolescent↗

Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.

UNLABELLED: We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. METHODS: Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. RESULTS: All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts.

Animals↗

Decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternal thymectomies.

BACKGROUND: We studied the incidences and evaluated the management of early postoperative complications after thymectomy for myasthenia gravis. METHODS: During the period between 1987 and 1996, 324 thymectomies were performed through median sternotomy access under general anesthesia. Postoperative management was administered according to a standardized protocol of anticholinesterase medication, which was withdrawn for the 48 hours of obligatory postoperative mechanical ventilation. The mean age of patients was 34 years (range, 8 to 71 years). RESULTS: One hundred forty-nine patients made an uneventful recovery; 104 patients had only minor complications, whereas 71 patients had major complications. The mortality rate was 0.6% (2 patients). The major surgical complications were recorded as sternal bleeding (1 patient) and sternal disruption (1 patient). The major general complications were recorded as tracheal stenosis (1 patient), pneumonia (3 patients), heart failure (1 patient), gastric hemorrhage (1 patient), and respiratory insufficiency (71 patients). Forty-six reintubations were performed on 40 patients and 19 tracheostomies (6%) were performed postoperatively. CONCLUSIONS: The excessive incidence of respiratory insufficiency and airway-associated morbidity was potentially related, at least partially, to prolonged mechanical ventilation and withdrawal of anticholinesterase medication. Earlier weaning of patients with revision of 48-hour withdrawal of anticholinesterase medication is necessary.

Adolescent↗

Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients.

BACKGROUND: Infrasternal mediastinoscopic surgery is a new approach to resection of the anterior mediastinal mass. METHODS: We evaluated this new approach in 23 patients with myasthenia gravis who underwent total thymectomy assisted by infrasternal mediastinoscopy between 1998 and 2000. The results were analyzed with special reference to morbidity and short-term improvement of the disease severity determined according to quantitative myasthenia gravis (QMG) scores. RESULTS: Complete removal of the thymic gland with the pericardial adipose tissue was accomplished through an infrasternal mediastinoscopic approach in 21 of the 23 (91.3%) patients. The remaining 2 patients required conversion to sternotomy, the one for insufficient sternal lifting with vascular tape and the other for invasion of a thymoma to the innominate vein. There was no related mortality and only one complication, a phrenic nerve injury in 1 patient (4.3%). Significant clinical improvement of disease was achieved in the short term and several advantages were apparent. CONCLUSIONS: Infrasternal mediastinoscopic thymectomy is safe and feasible for patients with myasthenia gravis.

Adult↗

Totally endoscopic robotic thymectomy for myasthenia gravis.

The current recommendations for treating myasthenia gravis include surgical thymectomy for patients between puberty and 60 years of age. This is a report of a new method for surgical thymectomy using the robotic da Vinci surgical system for a totally endoscopic approach. This new procedure combines the potential advantages of minimally invasive methods with the efficacy of open procedures.

Adult↗

Thymoma following transcervical thymectomy for myasthenia gravis.

A superior mediastinal thymoma was found in a patient two years following a transcervical thymectomy for myasthenia gravis. This case report illustrates another potential complication of incomplete thymectomy that may occur with the transcervical approach.

Female↗

Alfred Blalock and thymectomy for myasthenia gravis.

In 1936, Alfred Blalock performed the successful removal of a thymic tumor in a patient with myasthenia gravis. The patient experienced marked and sustained improvement for several years. Blalock prophesized then that exploration of the thymic region would be indicated in all patients with severe myasthenia gravis. A few years later, in 1941, he applied this theory by introducing thymectomy for nonthymomatous myasthenia and achieved similar improvement. Despite modern sophisticated knowledge about the disease and advances in thoracic surgical techniques, Blalock's original observations remain valid, and thymectomy has become a standard treatment for myasthenia gravis the world over.

History, 20th Century↗

The role of thymectomy in red cell aplasia.

Red cell aplasia is an unusual cause of anemia. Fifty percent of all patients with red cell aplasia will have a thymoma. Twenty-five to 30% of those who undergo thymectomy will be cured. Data are presented that suggest that any patient with red cell aplasia should have thymectomy through a median sternotomy. One of 3 such patients who underwent the operation has had complete remission for two years.

Aged↗

Thymectomy-induced deterioration of learning and memory in mice.

Male ddY mice were thymectomized 4 weeks after birth. Learning behaviors, tested in passive and active avoidance performances and in a spatial memory task, were significantly impaired in thymectomized mice at 10 months after thymectomy, in addition to the reduced immune response. Contents of hypothalamic norepinephrine and hypothalamic choline acetyltransferase activity were significantly increased in thymectomized mice. These results suggested that thymectomy at young adult life in mice not only impaired the immune response, but also deteriorated the learning and memory ability.

Animals↗