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PubMed1998

Postoperative infection after transsternal thymectomy for myasthenia gravis: a retrospective analysis of 125 cases.

The present study was conducted in an attempt to clarify the extent to which the preoperative severity of myasthenia gravis and immunosuppression favor postoperative infection. A retrospective analysis was carried out on 125 consecutive patients who had undergone transsternal thymectomy for myasthenia gravis between 1976 and 1995. The preoperative severity of myasthenia was graded by a modified version of Osserman's classification. The incidence of postoperative pneumonia among patients with Osserman's class 1, class 2, class 3, and class 4 disease were 0%, 10%, 21%, and 44%, respectively, showing a marked increase with the preoperative severity of myasthenia; however, postoperative wound infection and mediastinitis were unrelated to the preoperative severity of myasthenia. With every increment in Osserman class, there was an appreciable, though insignificant, rise in the frequency of preoperative immunosuppression. There was no significant association between postoperative infection and preoperative immunosuppression. These findings indicate that a poor preoperative clinical status has a greater impact on the risk of postoperative pneumonia than immunosuppression, and therefore, every effort should be made to decrease the preoperative severity of myasthenia. Promoting the widespread use of plasmapheresis seems particularly important for this purpose.

Adult↗
PubMed2002

Colon carcinoma after thymectomy for myasthenia gravis: report of a case.

A 74-year-old Japanese man was admitted to our hospital with anemia, 4 years after a thymectomy for thymoma associated with myasthenia gravis. A diagnosis of sigmoid colon carcinoma was confirmed, followed by surgical resection. This case is presented to reinforce that physicians should bear in mind the possibility of extrathymic malignancies in patients with thymoma.

Adenocarcinoma↗
PubMed1988

Sequential analysis of experimental autoimmune thyroiditis induced by neonatal thymectomy in the Buffalo strain rat.

We have studied the evolution of thyroiditis induced by neonatal thymectomy in Buffalo strain rats, with particular emphasis on the thyroid lymphocytic infiltrate. The earliest change was increased endothelial Ia expression, and infiltration of the thyroid at 5 weeks by ED1- and ED2-positive macrophages and B and T cells. The T cells comprised equal numbers of Ox 8 (T cytotoxic/suppressor)- and W3/25 (T helper)-positive cells. Ia-positive thyroid follicular cells were seen only in the presence of a T-cell infiltrate. Thyroglobulin antibody levels, thyroid weight, thyroid follicular cell Ia expression, and lymphocytic infiltration of the thyroid were maximal between Weeks 12 and 24, and impairment of macrophage function by injection of silica at this time produced amelioration of disease. The thyroid weight returned to control levels by Week 34 and Ia expression by thyroid cells disappeared. Circulating Ox 8-positive T cells were reduced between Weeks 12 and 24 and by Week 34 had returned to control levels. Our results indicate that the mononuclear infiltrate precedes thyroid follicular cell Ia expression and macrophages play an important role in perpetuating thyroiditis. Recovery from disease is accompanied by a return to normal in circulating suppressor/cytotoxic T cells.

Animals↗
PubMed1988

Immunologic and clinical studies on murine experimental autoimmune gastritis induced by neonatal thymectomy.

Experimental autoimmune gastritis (AIG), defined by the appearance of auto antibodies to parietal cells, was induced by neonatal thymectomy in BALB/c nu/+mice 3 days after birth. Vitamin B12 absorption and intrinsic factor in the stomach extract decreased compared with those in AIG-negative control groups. No decrease of the serum A/G ratio in AIG-bearing mice was observed. Although development of anemia, as evaluated by a decrease in hematocrit value, was poor until 12 mo of age and the gastric mucosa was hypertrophic, the AIG resembled human pernicious anemia rather than Ménétrier's disease. Adoptive transfer of spleen cells, but not sera, of AIG-bearing nu/+ into BALB/c nu/nu mice caused AIG in all animals 1 mo later, indicating the involvement of lymphocytes in the induction mechanism of AIG. Cytofluorometric and immunohistochemical analysis of lymphocytes in the gastric mucosa revealed T-cell infiltration at an early stage (1.5-3 mo) followed by B cell infiltration (6 mo). When the fraction enriched with parietal cells, which were intensively stained with sera of AIG-bearing mice and fluorescent antibody to mouse immunoglobulin G, was injected into the foot pads of AIG-bearing nude mice, typical delayed-type hypersensitivity reaction was observed in all animals. This was not seen in the mice injected with the cell fraction enriched with chief cells, although a few of them were stained by the immunofluorescent technique. Thus, the delayed-type hypersensitivity reaction seems to be directly involved in the mechanism of tissue damage.

Anemia, Pernicious↗
PubMed1989

Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies.

Autoimmune gastritis accompanied by autoantibodies to parietal cells was induced in BALB/c nu/+ mice by neonatal thymectomy 2-4 days after birth. Three monoclonal autoantibodies, designated as 2B6 (IgG1), 2G10 (IgG2b), and 1H9 (IgG1), were obtained from one of these mice. All three reacted specifically with parietal cells, 2G10 recognizing species-specific antigenic determinants and 2B6 and 1H9 recognizing interspecies-specific antigenic determinants. All three recognized antigens on the membrane of intracellular secretory canaliculi and the cytoplasmic tubulovesicular system of parietal cells. At least two different molecular groups were recognized by these antibodies; 2B6 recognizing a 65,000-79,000-mol wt group and 1H9 recognizing a 92,000-120,000-mol wt group. Sera of most mice with autoimmune gastritis reacted with either or both groups. Both groups were consistently coprecipitated by any of the three antibodies when solubilized in NP-40. Sera, from patients with pernicious anemia, containing anti-parietal cell antibodies could also precipitate these two groups of antigens. Competition assay and physicochemical studies showed that the epitopes recognized by the three monoclonal antibodies are different.

Anemia, Pernicious↗
PubMed1980

The pathological effects of immunosuppression of Schistosoma mansoni-infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with antithymocyte serum, and treatment with hydrocortisone acetate.

The effects of various immunosuppressive regimes on the survival and liver pathology of mice infected with Schistosoma mansoni were investigated. T-cell deprivation before infection (by adult thymectomy and subsequent anti-thymocyte serum administration), or treatment with hydrocortisone or cyclophosphamide or azathioprine after infection, all reduced survival of infected mice when compared with immunologically intact, infected mice. T-cell deprivation or steroids produced severe liver damage in infected mice despite a reduction in the size of the peri-oval granulomatous inflammatory reaction. Administration of chronic infection serum reduced liver damage in both T-cell-deprived and steroid-treated animals, but improved survival only in the deprived animals and not to the level seen in normal infected mice. The liver damage in immunosuppressed mice was not due to opportunistic bacterial infection. Thus, although immunosuppression reduced the granulomatous response to schistosome eggs in the livers of infected mice (as it does to eggs injected intravenously into the lungs), survival time was decreased. The relevance of these findings to human S. mansoni infections is discussed.

Animals↗
PubMed1983

T-lymphocyte and B-lymphocyte dichotomy in anuran amphibians: I. T-lymphocyte proportions, distribution and ontogeny, as measured by E-rosetting, nylon wool adherence, postmetamorphic thymectomy, and non-specific esterase staining.

We used sheep erythrocyte (SRBC) E-rosetting, nylon wool fractionation thymectomy and nonspecific esterase staining to assess T-lymphocyte characteristics in Rana pipiens during various developmental stages. T-lymphocytes appear in the spleens of premetamorphic tadpoles. We found significant levels of lymphocytes classifiable as T-cells in the peripheral blood of adults, but fewer numbers of T-cells in the thymus, jugular bodies, spleen, pronephros, mesonephros, liver and bone marrow. In addition, thymectomized Xenopus laevis showed a sharp decrease in T-cells as evidenced by E-rosetting, ANAE stain and nylon wool fractionation. The presence of T-lymphocytes in anuran amphibians and the existence of a receptor for SRBC on a population of these cells, suggest conservation of T-cells during evolution.

Age Factors↗
PubMedDate not supplied

Late thymectomy in Xenopus tadpoles reveals a population of T cells that persists through metamorphosis.

To investigate the persistence of larval T lymphocytes in the adult period, tadpoles of the South African clawed frog, Xenopus laevis, were allowed to develop to prometamorphic stages 57-58 and thymectomized (Tx). Thymectomy at this stage allows for maximal expansion of the larval T cell population but prevents emergence of the adult T cell population. Using a T cell-specific monoclonal antibody (mAb) which recognizes the XTLA-1 determinant, we examined the absolute numbers of thymic and splenic T cells expressing XTLA-1 in normal tadpoles, postmetamorphic Tx frogs, and intact age-matched adult frogs. A small, but measurable, number of larvally-derived XTLA-1+ cells persists through metamorphosis. By simultaneously staining with a mAb specific for class II major histocompatibility (MHC) antigens, we determined the phenotype of the persisting XTLA-1+ cells in the Tx frogs. Like XTLA-1+ splenocytes in intact adult controls which are predominantly class II+, most XTLA-1+ cells in Tx adults also express class II. In contrast, most XTLA-1+ cells in the tadpole are class II-. This suggests that a small population of class II+ larval T cells survives metamorphic transition to become a long-lived population in the adult. Alternatively, some class II- larval T cells may express class II in the adult period.

Animals↗
PubMed1993

Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy.

Control animals and rats infected 90 days earlier, by inoculation of 1 x 10(6) trypomastigotes of Trypanosoma cruzi at weaning, were subjected to adult thymectomy (ATx) or sham operation (S-ATx) and assessed 3 months later for the presence of myocardial lesions and levels of lymph node and spleen T-cell populations. Chronic focal myocarditis (CFM) developed in 78% and 84% of S-ATx or ATx infected rats, respectively. While the two groups of infected rats did not differ as to the occurrence of myocardial lesions, large foci of CFM were more prevalent in ATx infected rats. Chronic T. cruzi (Tc) infection resulted in decreased CD4+ and increased CD8+ lymph node and spleen cell, with CD8+ lymphocytes being lowered to normal values in the spleen of the ATx infected group. It is suggested that ATx might act by interfering with a down-regulating immunoregulatory mechanism, leading to an exacerbation of autoimmune reactions believed to be involved in the generation of myocardial damage.

Animals↗
PubMed1995

Post-thymectomy autoimmunity: abnormal T-cell homeostasis.

Thymectomy of 3-day-old mice induces organ-specific autoimmune disease, which is characterized by the presence of autoantibodies and T-cell infiltrates in the affected organs. Here, Adriana Bonomo and colleagues propose a new model for the pathogenesis of this syndrome, which integrates many of the homeostatic mechanisms of the immune system, including central and peripheral tolerance, T-cell maturation and exportation from the thymus, as well as lymphocyte recirculation and homing.

Animals↗
PubMed1984

The effect of steroids on the circulating lymphocyte population--VI. Studies of the thoracic duct T- and B-lymphocyte populations after neonatal thymectomy and prednisolone treatment. An immunofluorescence study in the rat.

The corticosteroid effect on circulating lymphocytes in a steroid-sensitive species (rat) was studied by immunofluorescence. Both normal and neonatally thymectomized animals were injected with a high dose of prednisolone. T- and B-lymphocytes as well as T-lymphocyte subsets were analyzed in thoracic duct lymph during the involution phase (3 h after injection) and the restitution phase (17 h after injection) using conventional and monoclonal antisera. Neonatal thymectomy significantly reduced the number of circulating T-helper and T-non helper cells. In the involution phase, after a corticosteroid injection, there was a 64% reduction of lymph cell content in normal rats, affecting both T- and B-lymphocytes. Thymectomized animals showed an even more pronounced disappearance of cells. Counted in percentage, more B- than T-lymphocytes disappeared from the circulation. The T-non helper cells disappeared to a greater extent than the T-helper cells did. Cells with Ia-antigen showed about the same values as the B-lymphocytes. During the restitution phase all cells types were restored to normal levels. It seems that a high prednisolone dose has a more pronounced effect on the circulation of B- than of T-lymphocytes, and the T-non helper cells are probably more sensitive than the T-helper subpopulation. These data support the hypothesis that a major corticosteroid effect is a trapping and redistribution of circulating lymphocytes, more pronounced for certain cell types.

Animals↗
PubMed1992

The influence of neonatal thymectomy on the development of radiation myelopathy in rats.

To investigate the possible contribution of cellular immunity in the development of radiation injury of the central nervous system, Wag/Rij rats were thymectomized at birth and irradiated to the cervical spinal cord at the age of 3 months. At the time of paralysis or at the end of the follow-up period (when rats were 1-year-old) the animals were sacrificed and the mediastinum was examined histologically. In 95% of the neonatally thymectomized animals no thymus was left. These rats showed a firm impairment of the cellular immunity, as they had a 40% reduction of the T-lymphocytes in the spleen, and a 70% reduction of the mixed lymphocyte reaction, compared to age-matched controls. Both single dose and two-fraction irradiation experiments were performed. No modification of the latency time to develop paralysis was observed comparing thymectomized and age-matched controls. The incidence of foreleg paralysis after cervical spine irradiation (single dose or two-fraction) was identically distributed in the follow-up period for both neonatally thymectomized and control Wag/Rij rats. The ED50 value derived in the single dose experiments was 20.3 Gy for the control animals, and 20.9 Gy for thymectomized rats, and in the two fraction experiments 29 Gy for controls and 29.6 Gy for thymectomized rats. None of these differences are significant. It appears that neonatal thymectomy, in spite of its firm suppression of the cellular immunity, has no major influence on the development of radiation myelopathy in rats.

Animals↗
PubMedDate not supplied

Total intravenous anesthesia with propofol for transsternal thymectomy in myasthenia gravis.

Patients with myasthenia gravis (MG) represent a significant management problem for the anesthesiologist. Anesthetic concerns center on the MG patient's unpredictable response to muscle relaxants and increased susceptibility to postoperative respiratory failure, resulting in prolonged dependence on mechanical ventilation. We describe the first reported use of total intravenous anesthesia with propofol to provide satisfactory surgical conditions in two patients with MG undergoing trans-sternal thymectomy. Propofol is a suitable drug for intubation and continuous infusion anesthesia, allowing fine control of anesthetic depth, good operating conditions, and a recovery profile suitable for MG patients undergoing surgery.

Adult↗
PubMed1989

Thymectomy in myasthenia gravis. Results of 662 cases operated upon in 15 years.

The results of thymectomy in the treatment of myasthenia gravis (MG) are reviewed in the light of a personal series of 662 MG patients, operated upon during the last 15 years. In 500 MG patients without thymoma, the following results have been achieved: remission 37.9%, improvement 49.4%, unchanged or worse 7.4%, dead 5.2%. There is no sex prevalence and the remission rate is higher in patients under 40 years of age (P less than 0.01), with mild disease (P less than 0.05), with a MG duration of less than 1 year (P less than 0.05) and with a follow-up length of between 5 and 10 years (P less than 0.01). No correlations are found between outcome and thymic histology. The results of 162 MG patients with thymoma are: remission rate 15.7%, improvement 60.3%, unchanged or worse 3.7% and dead 20.1%. The remission rate is higher with mild symptoms (P less than 0.05) and when the tumour is encapsulated (P less than 0.02). The postoperative mortality is 0.8% (none in the last 5 years) for non-thymomatous MG and 4.9% for thymomatous MG (2 of 8 patients died of pancytopaenia and 1 of pulmonary embolism).

Adolescent↗
PubMed2005

Trans-arterial infusion chemotherapy for recurrence of pleural dissemination after thymectomy.

We present a report of trans-arterial infusion chemotherapy through the intercostal arteries and subphrenic artery for pleural dissemination of recurrent thymoma after thymectomy. The disseminated tumor did not enlarge for more than a year after this treatment, and there were no side effects. Trans-arterial infusion chemotherapy appears to be a preferable procedure for pleural dissemination of thymoma.

Aged↗
PubMed2006

Immune system and bone metabolism: Does thymectomy influence postmenopausal bone loss in humans?

Recent studies of animal models have suggested that an increase in the number of T cells due to both peripheral expansion and increased thymic T cell output plays a key role in the regulation of bone loss after ovariectomy. Osteoclastogenic cytokines which are either produced by T cells or activate T cells have also been implicated in ovx induced bone loss. Among them are TNF alpha and IL-7. The present study investigates the role of thymectomy (THX) and IL-7 in bone metabolism in humans. We studied T cells subsets, cytokine production and bone metabolism in 13 women thymectomized for Myasthenia gravis as compared to healthy controls. Our data demonstrate that the number of CD4+ and TNF-producing T cells is lower in THX women as compared to euthymic controls. However in THX women the residual T cells produce higher levels of IL-7 and RANKL. Furthermore, flow cytometry shows that IL-7 is produced by T and B cells. Serum levels of TNF alpha were unaffected by THX and both serum TNF alpha and the RANKL/OPG correlated inversely with BMD. There were no differences in bone turnover and bone mineral density between THX women and the controls. These data suggest that THX decreases the number of TNF-producing CD4+ T cells but does not alters serum TNF levels. The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL. Further studies are needed to clarify the role of thymus in bone metabolism and osteoclastogenesis in postmenopausal women.

Adolescent↗
PubMed2004

Increase of circulating CD4+CD25+ T cells in myasthenia gravis patients with stability and thymectomy.

BACKGROUND: CD4(+)CD25(+) regulatory T cells are key controllers of peripheral immunological self-tolerance and suppress various autoimmune diseases in animal models, but few studies have been done to define their roles in myasthenia gravis (MG) so far. OBJECTIVE: To investigate frequencies and dynamic changes of blood CD4(+)CD25(+) T cells from MG patients. METHODS: The peripheral blood CD4(+)CD25(+) T cells of 29 MG patients and 23 healthy controls were detected by three-color flow cytometry. RESULTS: Myasthenic patients with symptomatically uncontrollable disease showed slightly lower percentages of CD4(+)CD25(+) T cells (mean = 3.79 +/- 1.40%; P = 0.12), whereas MG patients with clinically stable disease had significantly increased CD4(+)CD25(+) T cells (mean = 8.45 +/- 1.96%, P = 0.0001), as compared with healthy controls (mean = 4.53 +/- 0.96%). In addition, thymectomized MG patients had significantly higher percentages of CD4(+)CD25(+) T cells (mean = 8.44 +/- 2.39%), as compared with both non-thymectomized MG patients (mean = 5.88 +/- 2.89%, P = 0.038) and healthy controls (P = 0.003). CONCLUSIONS: Our observations indicate that increased percentages of CD4(+)CD25(+) T cells in MG patients may be related to disease stability and that thymectomy in patients with MG resulted in augmented CD4(+)CD25(+) T cells.

Adolescent↗
PubMed2005

Low-dose tacrolimus for two cases of myasthenia gravis with invasive thymoma that relapsed shortly after thymectomy.

Two patients with myasthenia gravis (Ossermann IIb) involving invasive thymoma who underwent extensive thymectomy manifested myasthenic crisis shortly after the procedure; however, both patients were treated with intravenous immunoglobulin and recovered from myasthenic crisis that had been deteriorating for about 1 week. Subsequently, the patients were administered a low-dose of tacrolimus (3 mg/day) in addition to prednisolone. Several months later, tacrolimus continued to control fluctuations of myasthenic symptoms and maintained remission in these patients. The serum titer of anti-Ach-receptor antibodies decreased in parallel with clinical improvement due to tacrolimus, and we accordingly reduced the dosage of prednisolone. Tacrolimus is a new immunosuppressive agent acting through the selective inhibition of helper-T-cell activation that can be reduced dosage of steroids and can maintain remission of myasthenia gravis with invasive thymoma.

Adult↗