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PubMed1990

[Myasthenia gravis: results of thymectomy in 550 patients].

Report is giving on 550 myasthenic patients who underwent thymectomy during the last 18 years. Results of thymectomy are analysed in separate groups and according to different aspects, including thymic tumours (13.63%), operations in childhood (9.64%), and combined cases (11.1%). The results are evaluated according to Disability Status Scale based on a point-system. Successive improvement was observed in the three series concerning the results of operation. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined group, in long-lasting myasthenia and in tumourous cases, too. There are quite a few factors influencing the results, such as the interval between the disease onset and thymectomy, the patients' age, thymoma, crisis-danger and the activity of the thymus gland reflecting in the number of the germinative centres. The more active the thymus, the better the results.

Humans↗
PubMed1986

[Significance of thymectomy in the treatment of myasthenia gravis pseudoparalytica in a patient sample in Bern].

A retrospective assessment has been made of the medium to long-term outcome in 40 consecutive patients with myasthenia gravis in whom thymectomy was performed. Treatment of myasthenia gravis, when combined with thymectomy, was associated with a 40.6% complete remission rate and with partial remission in 43.8% of our cases, provided no thymoma was present. In the latter cases (n = 8) the results of surgical treatment were significantly poorer. This is in accordance with other reports in the literature. Based on our experience we are convinced that radical extended thymectomy, including resection of neighbouring mediastinal fat tissue, using longitudinal sternotomy for access, is the method of choice. This mode of treatment has been advocated by a number of authors in recent years, and we have reason to believe that this therapeutic concept will give rise to improved results in the patient group with thymoma also. In our series, such factors as sex, age and time interval between onset of disease and operation date were of minor importance and had no significant prognostic value. Due regard must of course be paid to the unspecific risks associated with age. Operative thymectomy is indicated whenever myasthenia gravis is diagnosed, with the exception of those cases presenting with ocular symptoms alone (group 1 of Osserman's classification).

Adolescent↗
PubMed1979

Effect of thymectomy on tumor development and on T and B lymphocytes in tumor-bearing rats.

Tumor growth and changes in T and B lymphocyte ratio in spleen, draining lymph node and peripheral blood of thymectomized, irradiated rats, reconstituted with syngeneic bone marrow transplanted at various time intervals with MC-1 fibrosarcoma cells were followed. Control nonthymectomized or "sham" operated rats were transplanted an equal dose of tumor cells. Thymectomy and irradiation reduced the numbers of T lymphocytes in all lymphoid organs, while the enhanced numbers of B cells are probably related to reconstitution with cells of syngeneic bone marrow. The time interval between thymectomy, irradiation and transplantation of tumor cells proved to be a limiting factor for tumor growth and changes in T and B cell ratio. Early transplantation of tumor cells (7 days after irradiation) resulted in an enhanced resistance to tumor development, a reduced tumor growth rate and a progressing decline in the number of T cells. If the interval between thymectomy and tumor cell transplantation lasted 4 weeks, the T cell population became partially regenerated, and tumors grew progressively in correlation with a continuing T lymphocyte depletion. The results are discussed in terms of the role of various T cell subpopulations and the significance of residual, thymectomy- and irradiation-resistant T lymphocyte population, vital for a preservation of T cell immunological functions.

Animals↗
PubMed1985

Anti-acetylcholine receptor antibody titer with extended thymectomy in myasthenia gravis.

Twenty-four patients with myasthenia gravis of Osserman's generalized type underwent extended thymectomy through a sternal-splitting approach. Their clinical responses to thymectomy and postoperative changes in anti-acetylcholine receptor antibody titers were evaluated. The follow-up time ranged from 1 month to 7 years and 7 months (average, 36 months). Six patients (25%) had remissions and 17 patients (71%) were improved after operation. The preoperative anti-acetylcholine receptor antibody titers dropped significantly after operation (p less than 0.001). The postoperative reduction in these titers correlated with the time course after operation (p less than 0.05). Their postoperative reduction was significantly greater in the six patients having remissions than in the 15 having marked (p less than 0.02) and the six having moderate improvement (p less than 0.005). This study has revealed that anti-acetylcholine receptor antibody titer in plasma declines progressively after thymectomy, and the postoperative reduction of this titer correlates with the clinical effect of thymectomy.

Adolescent↗
PubMed1979

[Morphological changes in the myocardium after thymectomy].

The authors followed in dynamics the systolic arterial blood pressure and morphometric changes in the myocardium (cardiac, index, mean number of myocardial cells per unit of area c I mm2, mean diameter of the myocardial cells of the papillary muscles and subendocardial laer of the left ventricle) in thymectomized and sham thymectomized rats. The studies were made after thymectomy and sham thymectomy on the second, sixth, twelfth and sixteenth week. The systolic arterial blood pressure in thymectomized rats was elevated gradually and reached up to 170 mmHg on the sixteenth week, but it was in normal ranges in sham thymectomized animals. The cardiac index and mean diameter of the myocardial cells were larger in thymectomized rats, but the mean number of cells was smaller in comparison with sham thymectomized animals-results showing development of myocardial hyperthrophy after thymectomy. The induced myocardial changes were probably of adaptive character and could be due to neurohormonal mechanisms and hemodynamic loading of the heart becuase of the elevated arterial blood pressure after thymectomy.

Animals↗
PubMed1980

Effects of intrauterine thymectomy on mitogen response in guinea pig.

Intrauterine thymectomy was carried out on days 36, 40, 48 and 68 (neonatal) of foetal life to investigate the role of thymus and emigration of thymocytes in the development of mitogenic (PHA, Con A, DxS) responses in the guinea pig. The results provide further evidence that emigration of thymocytes is a continuous process which takes place already at the time of demarcation between thymic cortex and medulla (before day 36 of gestation) and again immediately after birth. In the lymph nodes of guinea pigs thymectomized on day 36 in utero a small PHA and Con A responding cell population exists at the time of birth but not any more 3-4 mth later. This population is considered to depend on the transplacental thymic product(s). However, spleen and blood lymphocytes of animals thymectomized on day 36 in utero respond to PHA and Con A to some extent at the age of 3-4 mth, suggesting that the population emigrating before day 36 has a longer survival in the spleen and blood than in lymph nodes. Thymectomy at 40 days of gestation leaves an additional population which can express a good PHA and Con A response even in lymph nodes without a direct thymic influence. Responses to DxS were not significantly affected by the intrauterine thymectomy. Thus, intrauterine thymectomy at 36 days of gestation induces a severe but not complete T cell depletion in the guinea pig.

Animals↗
PubMed1984

Cervical thymectomy in the treatment of myasthenia gravis.

A retrospective review of 22 patients undergoing cervical thymectomy for myasthenia gravis is presented. Their ages ranged from 19 to 67 years. The male and female ratio as well as the severity of illness prior to operation were similar to other reported series. All patients were evaluated from the standpoint of clinical response to thymectomy, and the number and dosage of anti-myasthenic drugs required after operation. There was a statistically significant improvement in clinical status in the immediate postoperative period (P less than 0.05) and a further significant improvement was noted at six months (P less than 0.05). In addition, significant reductions in postoperative drug therapy were noted (P less than 0.05). Complications from cervical thymectomy were minimal and mortality was zero. An attempt was made to correlate histological findings with clinical results. Comparison is made to other series in the literature and the advantages of the cervical technique as the initial surgical approach are described. The data presented support a useful role for cervical thymectomy in the treatment of myasthenia gravis.

Adult↗
PubMed1984

[Thymectomy in myasthenia gravis pseudoparalytica].

From 1967 to 1982, 109 thymectomies were performed mainly in patients with moderate severity of the disease. The age of patients averaged 30,3 years. Operative lethality amounted to 2.7%. Another 4 patients died of the basic disease 6 months after the operation. During the subsequent course 70% of the patients showed a longlasting improvement after thymectomy, with complete recovery occurring in 23% and a significant amelioration in 40% of thymectomized patients. In another 32% there was a slight improvement of complaints. The best results could be observed in myasthenic patients with thymic hyperplasia whereas only a slight remission occurred after removing thymomas. 5 to 10 years after thymectomy the improvement rates remained approximately at the same level. Consequently, thymectomy can be regarded as a successful therapy in myasthenia gravis pseudoparalytica.

Adolescent↗
PubMed1983

Induction of autoimmunity in normal mice by thymectomy and administration of polyclonal B cell activators: association with contrasuppressor function.

In order to gain insight into the role of polyclonal B cell activation in the development of autoimmunity, non-autoimmune mice were given chronic injections of polyclonal B cell activators (PBA). In addition, to assess the contribution of T cell regulation of such PBA-induced B cell hyperactivity, the additional effect of postnatal thymectomy was studied. Mice that were postnatally thymectomized and given PBA (LPS +/- poly rI X rC) thrice weekly were found to have elevated levels of IgG and significantly increased serum concentrations of anti-ssDNA. This anti-DNA production was greater than that observed with PBA alone or with thymectomy alone. The entire experiment was repeated with different non-autoimmune mice with the same result. Numbers of proliferating cells in the spleens of the mice in the various groups were analysed by flow cytometry. The number of cells in S+G2+M phases of the cell cycle was significantly increased by PBA or thymectomy alone as well as by the combination. As a result, B cell proliferation was not sufficient to result in maximal anti-ssDNA; an additional T cell defect was required. This was further studied in an in vitro assay for suppressor and contrasuppressor activity. In three separate experiments, mice which were clinically autoimmune were found to have defective suppressor function and the presence of abnormal contrasuppressor activity, whereas non-autoimmune controls had normal suppressor function and no contrasuppressor function. These results indicate that the combination of PBA and thymectomy can most easily induce autoimmunity. The autoimmune state so induced in non-autoimmune strains was associated with a failure of normal suppressor function and the abnormal presence of contrasuppressor function. These results have important implications for spontaneously occurring autoimmune diseases.

Animals↗
PubMed1980

Influence of adult thymectomy on immunocompetence in patients with myasthenia gravis.

The influence of adult thymectomy on several parameters of immunocompetence in patients with myasthenia gravis (MG) was investigated. Since incomplete thymectomy may lead to the presence of thymic remnants, we determined the activity of a thymus-dependent factor in the sera of the MG patients. As measured by several parameters, MG patients showed a normal immunocompetence compared with healthy controls, except in the response to DNCB sensitization in vivo. When tested at least 5 years after thymectomy, MG patients were found to have decreased response to mitogens, and a decreased cytotoxic T cell response in cell-mediated lympholysis. The response to challenge with DNCB in vivo was decreased both in thymectomized and nonthymectomized MG patients. No difference was found in a) the percentage of circulating T, B, non-B/non-T cells; b) the response to allogeneic cells (MLR); c) the antibody-dependent lymphocytotoxicity; d) the production of immunoglobulins in vitro by pokeweed mitogen-stimulated cells; and e) the anamnestic response to antigens in vitro. We conclude that adult thymectomy results in a decrease in the function of some subpopulations of lymphocytes.

Adult↗
PubMed1980

Effects of thymectomy on bone growth in the rat.

The effects of thymectomy (TMX) at 1 or 5 days of age on the subsequent growth of bone have been determined in male and female Holtzman rats. The rats were maintained under aseptic conditions to minimize any effects of infection or wasting disease on bone growth. Femur length and distal epiphyseal cross sectional area were significantly reduced in TMX female rats at 3 months of age. At 1 month of age, the width of the undifferentiated zone was increased and at all subsequent times the columnar zone and growth plate were narrower in TMX rats. The incorporation of 35S into the femur, particularly the proximal and distal growth plates, was uniformly reduced in TMX rats as determined by scintillation counting and autoradiography. Additionally, there was an obvious overall reduction in alcian blue stationing intensity in the growth plates of TMX rats when compared to sham-operated controls. These results suggest a significant reduction in detectable glycosaminoglycan (GAG) content and in bone growth in TMX rats. Although there were minor variations, there were no major differences attributable to sex or timing of thymectomy. At present the causes of this moderate reduction in bone growth in TMX rats are unknown. One explanation might be that the thymus supplies or is in some other way involved in the provision of a hormone and/or cells that are required for normal bone growth. Another possibility is that the thymus is normally a source of immune suppressor cells which are needed to limit auto-immune reactivity against GAG or other antigenic determinants associated with bone. Thymectomy would remove these suppressor cells, thus permitting an auto-immune response which interferes with bone growth. Finally, perhaps the most plausible explanation is that thymectomy reduces cell production in the bone marrow which, in particular, reduces the turnover of monocytes. This reduced output of monocytes in TMX rats might ultimately lead to a reduction in osteoclast activity necessary for normal remodelling and growth of bone. We currently favour this last explanation.

Age Factors↗
PubMed1981

Effects of adult thymectomy on the contact sensitivity skin reaction and the unresponsiveness caused by feeding contact sensitizing agents.

Unresponsiveness was produced in mice by three feeds of high doses of oxazolone or picryl chloride. The mice were then sensitized and contact sensitivity assessed by ear swelling. Adult thymectomy prevented the unresponsiveness caused by feeding. In some but not all experiments adult thymectomy also increased the response to a single skin paint. This effect of thymectomy was apparent at 1 week and reached a plateau at 2-3 weeks. The effect of adult thymectomy, on unresponsiveness caused by feeding and its ability to increase the contact sensitivity skin reaction, was reversed by treatment with crude thymosin fraction V.

Animals↗
PubMed1995

Major long-term changes in gamma delta T-cell receptor-positive and CD2+ T-cell subsets after neonatal thymectomy in the pig: a longitudinal study lasting nearly 2 years.

Blood leucocyte subsets in neonatally (20-day-old) thymectomized (Tx) and sham-thymectomized (STx) pigs were analysed 13 times over nearly 2 years. Tx piglets showed a persistent selective leucopenia, due mainly to a approximately 95% reduction in gamma delta null T cells which fell, with a circulating half-life of approximately 2 weeks, to approximately 0.3 x 10(6)/ml. This residual population was extrathymic in origin since it increased numerically at least approximately eightfold as the Tx pigs grew. Changes in other subsets were complex and affected by antigenic experience associated with weaning and with a change of accommodation at approximately 4 months postoperation (p.o.). Most major populations were increased long-term after thymectomy, especially after 3 months p.o. [i.e. surface (s)IgM+ B cells and CD2+, CD8+, major histocompatibility complex (MHC) class II+, CD4+ and double-positive CD4+ CD8+ T-cell subsets]. However, during the first 3 months, thymectomy caused a significant delay in development of CD8high and CD4+ T cells and, after 4 months p.o., a continuing lack of CD4only (single-positive) T cells. Fortuitous environmental antigenic stimulation caused a major transient lymphocytosis, with counts increasing 1.2-fold in STx and 3.5-fold in Tx pigs. This was largely due to an increase in CD2+ CD8+ MHC class II+ T cells, particularly in Tx pigs. The small residual thymus-independent gamma delta null subset also increased, while gamma delta T cells in STx pigs actually decreased. Evolving changes in expression of CD45, CD45R, CD44, CD18 and very late antigen type-4 (VLA-4) also occurred following thymectomy. Thus, the most persistent long-term effect of thymectomy, other than the lack of gamma delta null T cells, was the markedly increased numbers of double-positive (CD4+ CD8low) T cells, most of which expressed MHC class II and higher levels of adhesion molecules.

Animals↗
PubMed1995

[Development of myasthenia gravis after thymectomy for thymoma].

Impaired neuromuscular transmission in myasthenia gravis is caused by autoimmune mechanisms. The association of myasthenia gravis with pathological abnormalities of the thymus has been known for a long time and was the reason why thymectomy was used in the treatment of myasthenia gravis before the immunocompetent impact of the thymus and the autoimmune pathogenesis of myasthenia was known. Forms of myasthenia refractory to thymectomy, and in particular the development of myasthenia gravis after thymectomy on account of a thymoma, indicate the fact that in case of destruction of postsynaptic acetylcholine receptors an important part is played by extrathymic humoral and cellular autoimmune mechanisms. In the submitted paper the authors describe three patients where myasthenia gravis was manifested several months to 14 years after thymectomy on account of a thymoma. The presented facts emphasize the importance of immunosuppressive treatment of patients with myasthenia gravis.

Adult↗
PubMedDate not supplied

[Usefulness of plasmapheresis before thymectomy in the management of myasthenia gravis].

Plasmapheresis (PMP) is effective in some clinical situations of myasthenia gravis (MG). To evaluate its usefulness before thymectomy in patients with moderate generalized MG with no respiratory involvement, we studied 24 patients with MG divided into 2 groups of 12. PMP was performed before thymectomy in one group. The course of disease and mean doses of drugs required were recorded over a follow-up period of 12 months. There were no significant differences between the 2 groups in clinical condition or mean dose of anticholinesterase agents before or after thymectomy. Significantly higher doses of corticosteroids were used after the third month of follow-up in the group treated with PMP. We conclude that PMP confers no benefit when applied before thymectomy in patients without severe MG.

Adolescent↗
PubMedDate not supplied

Thymectomy in over 50 years-old patients with myasthenia gravis: long and short-term results in 21 patients.

Thymectomy is considered to be an important method for the treatment of myasthenia gravis in older patients when the improvement cannot be achieved with the use certain drugs such as anticholinesterasic, corticosteroids and immunosuppressive agents. In our series of 281 thymectomized patients, 13 were male and 8 female, varying their age between 50 and 73 years. The duration of the disease prior to the thymectomy varied between 30 days and 15 years; in 12 of them (57%) it lasted already 2 years. Eleven patients had the severe and eight the moderate clinical form of the disease. Nine patients were treated with corticosteroids before submitted to thymectomy. In 11 patients the histopathological changes in the thymus were evaluated: eight had thymomas, one atrophic changes, one lipomatosis and one a normal thymus. The short-term follow-up revealed important improvement in 12 patients, slight improvement in four and worsening in two; two patients died. It is concluded that thymectomy may be indicated in older patients when their condition worsens in spite of the use of corticosteroids and immunosuppressive agents, in the presence of serological markers or computerized tomography image indicating thymoma, and intolerance for corticosteroids.

Aged↗
PubMed1977

Effects of thymectomy on the endocrine glands of the rat.

The effects of thymectomy on the thyroid gland, the adrenal cortex, the testes and the lymph nodes of the rat follow the same pattern as those observed in guinea pigs but in a very attenuated form. Thymectomized rats do not show the wasting observed in thymectomized guinea pigs. The effects on the adenohypophysis are approximately the same in rats and guinea pigs, but the sequence of the changes is different. Injections of thymic extract or of presumably pure thymic hormone suppressed all the effects of thymectomy on the endocrine glands of the rat. In rats, thymic hormone was found in the thymus, the lymph nodes and the spleen. It disappeared from the lymph nodes and the spleen within three days of thymectomy and did not reappear, although most of the changes in the endocrine glands were transitory. The implications of the observations for understanding the consequences of thymectomy are discussed.

Adrenal Cortex↗
PubMed1997

Benefits of early thymectomy in patients with myasthenia gravis.

OBJECTIVE: To report our experience of early thymectomy in patients with myasthenia gravis. DESIGN: Retrospective study. SETTING: University department of surgery, Greece. SUBJECTS: 76 Patients with myasthenia gravis. INTERVENTIONS: Transcervical thymectomy in all cases, additional left thoracotomy in four cases. MAIN OUTCOME MEASURES: Mortality, morbidity, and early (6 months) and late (mean follow-up 4.8 years) response to thymectomy. RESULTS: 20 Patients had thymomas (26%). There was no postoperative mortality; morbidity was 11% (n = 8). There was complete remission in 19 (25%), improvement in 49 (65%) no change in 7 (9%), and impairment in 1 (1%) of the patients at 6 months. Patients who had had symptoms for less than 5 years (p < 0.001), were in an earlier stage of disease (p = 0.006), and who did not have thymomas (p = 0.006) responded better. 3 Patients died of invasive thymoma at 2 1/2, 3, and 5 1/2 years postoperatively and 25/76 (33%) were lost to follow-up. Of the 51 patients available for late follow-up, 19 (37%) were in remission, in 26 (51%) the symptoms had improved, 3 (6%) were unchanged, and 3 (6%) had died of the disease. CONCLUSIONS: Transcervical thymectomy should be considered in patients with early myasthenia gravis.

Adult↗