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PubMed1976

Adult thymectomy prevention of the appearance of suppressor T cells which depress contact sensitivity to picryl chloride and reversal of adult thymectomy effect by thymus extract.

Suppressor cells, which depress the passive transfer of contact sensitivity appear in the lymph nodes and spleen of mice injected with picryl sulfonic acid (PSA). These cells produce a soluble suppressor T cell product (s-TCP), and immune lymph node cells incubated in s-TCP fail to transfer contact sensitivity. This paper shows that the appearance of suppressor T cells following the injection of PSA was prevented by adult thymectomy (ATx). ATx also limited the production of s-TCP. However, ATx had no effect on the DNA synthesis which occurs in the lymph nodes of mice injected with PSA. The adverse effect of ATx on suppressor cells was completely reversed by a neonatal thymus graft placed under the renal capsule and partially reversed by grafts given 600 r in vitro and to a limited extent by grafts given 1000 r. The injection of thymus extract also reversed the effect of ATx whereas splenic extract was inactive. It is suggested that the suppressor T cell which depresses contact sensitivity is dependent on the presence of the thymus because it requires a thymus hormone, and not primarily because it belongs to a short-lived population which is rapidly renewed by cells coming from the thymus.

Animals↗

PubMed1975

Studies in myasthenia gravis: early thymectomy. Electrophysiologic and pathologic correlations.

Indications for thymectomy in myasthenia gravis have been recently expanded to include all cases with extraocular symptoms as a result of the minimal morbidity and negligible mortality of the transcervical approach. As increasing numbers of patients with myasthenia gravis, covering the entire spectrum of generalized disease, have been added to the thymectomy population, a more accurate evaluation of the effects of the operation is possible. Our experience with 353 patients who have undergone thymectomy indicates that early thymectomy, particularly in patients who do not have germinal centers, is followed by early remission of the disease. Delayed remission after thymectomy is related to the duration and severity of the disease, and to presence of thymic germinal centers. Germinal centers were found more frequently in patients with long duration of the disease and in patients in whom the disease had progressed to respiratory involvement. Marked improvement in electromyographic findings immediately after thymectomy was observed in the majority of patients who had had the disease for 1 year of less and where germinal centers were absent. The percentage of malignant thymomas was higher in patients who underwent thymectomy 1 year or more after the onset of symptoms of myasthenia gravis. These data indicate the importance of early thymectomy while the disease is still in the mild stages. Transcervical thymectomy is the treatment of choice as it is followed by a higher percentage of remissions and by less morbidity than other forms of treatment.

Adolescent↗

PubMed1979

The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats.

The objective of these experiments was to determine the effects of neonatal thymectomy on the induction of experimental autoimmune orchitis in inbred rats of the Fischer 344 and Lewis strains. It was found that thymectomy alone in Lewis rats, and thymectomy followed by immunization with testicular extract in both Lewis and Fischer 344 rats, led to the development of autoimmune orchitis, as indicated by decreased testes weights, increased serum spermagglutinating antibody titers and histopathological changes in the testes. These data indicate that rats of the Lewis strain are genetically predisposed to the development of autoimmune orchitis, and thymectomy alone leads to active manifestations of the disease, which are further enhanced by subsequent immunization with testicular extract. In Fischer 344 rats, thymectomy followed by immunization leads to indications of early signs of experimental autoimmune orchitis. This is in contrast to experimentally induced autoimmune diseases in other model systems, where previous investigators have reported that thymectomy lessens or prevents induction of autoimmune disease. It is suggested that these differences may be related to the timing of thymectomy with regard to differences in the time of appearance of sperm antigens (at puberty) as compared to pre-natal and early neonatal appearances of other autoantigens.

Animals↗

PubMed1975

Transcervical thymectomy in myasthenia gravis.

Since 1967, transcervical thymectomy has been the procedure of choice for all patients with nonthymomatous myasthenia gravis and a selected group of patients with thymomatous myasthenia gravis operated upon at the Mount Sinai Hospital. A total of 180 transcervical thymectomies have been performed. In 12 patients, a pre-existing tracheostomy was present. Morbidity was minimal, limited to three instances of bleeding, five of pneumothorax, one of self-limited chylothorax, and one wound infection. One postoperative death from an unrelated cause occurred in 1967. The postoperative course has been smoother and the management of the myasthenia gravis considerably easier than those following transthoracic approaches. Consequently, routine elective tracheostomy at the time of thymectomy has been abandoned. The average period of hospitalization does not exceed one week. As a result of the minimal risk involved, indications for thymectomy now include all patients with generalized myasthenia gravis, and the procedure is performed earlier in the course of disease. Postoperative electromyographic findings show immediate improvement in the majority of patients operated upon during the first year in which symptoms occur. Transcervical thymectomy arrests the progress of the disease, decreases the mortality rate, and has long term results equal to those of transthoracic approaches. Earlier remissions, fewer germinal centers, and a smaller number of thymomas were noted in patients operated upon early in the course of the disease. A decrease in neoplasms outside the thymus gland and in neonatal myasthenia gravis was also noted following thymectomy.

Breast Neoplasms↗

PubMed1977

Lymphocyte-mediated cytotoxicity: effects of ageing, adult thymectomy and thymic factor.

Adult thymectomy, as well as ageing, depressed splenic lymphocyte-mediated cytotoxicity (LMC) in the mouse. Ageing depressed significantly LMC as early as 19 weeks of age, independently of the number of cells used for immunization. Thymectomy affected LMC only when supoptimal numbers of immunizing allogeneic cells were used. This effect peaked at 6 to 12 weeks after thymectomy. No difference between thymectomized and normal mice was observed when LMC was tested 16 to 20 weeks after thymectomy, at an age when normal control mice themselves already showed a lowered LMC due to ageing. The effect of in vivo treatment with a circulating thymic factor (TF), which was shown to disappear with ageing as well as after adult thymectomy, has been tested in adult thymectomized mice and normal young and ageing mice. TF treatment prevented LMC depression in adult thymectomized mice, whereas it depressed paradoxically splenic LMC in normal young and old mice. The possible mechanisms of the effects of adult thymectomy, ageing, and thymic factor on the different T cell subsets involved in allogeneic killer cell generation are discussed.

Aging↗

PubMed1978

Thymectomy in patients more than forty years of age with myasthenia gravis.

Until recently, thymectomy has been reserved for patients with myasthenia gravis in the younger age groups. The use of transcervical thymectomy, with its reduction in morbidity and mortality, has allowed us to study the effects of thymectomy in the older age group. The records of 525 patients who underwent thymectomy were reviewed and divided into two groups: those less than and those more than 40 years of age. The incidence of thymomas was greatest in the older than 40 year group. This age group without thymoma was also noted to have a high incidence of absent germinal centers. The postoperative remission rates as well as the electromyographic improvement rates were comparable for both age groups. The evidence presented indicates that thymectomy improves the clinical course of myasthenia gravis in all age groups studied. We recommend transcervical thymectomy for all patients with generalized myasthenia gravis, regardless of age.

Adult↗

PubMed1975

Transcervical thymectomy in renal transplant recipients: surgical complications and possible effect on long-term allograft survival.

Between January 1963 and December 1967, 59 renal transplant recipients underwent thymectomy with or without splenectomy as an adjuvant to standard immunosuppression. All thymectomies were performed transcervically. By internal comparison long-term renal allograft survival was better in recipients who had thymectomy, when compared to those who did not. There were no significant surgical complications associated with transcervical thymectomy and the completeness of thymectomy was judged satisfactory. The role of thymectomy as an adjuvant operation in human renal transplant recipients should be re-examined.

Cadaver↗

PubMed1979

Humoral immunity before and after thymectomy in myasthenia gravis.

Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p less than 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p less than 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.

Adult↗

PubMedDate not supplied

Anesthesia for transcervical thymectomy in myasthenia gravis.

This review of anesthetic experience in 100 cases of transcervical thymectomy for myasthenia gravis (MG) at The Mount Sinai Hospital (1970-1974) underlines current trends in the surgical management at Mount Sinai, where transcervical thymectomy is the procedure of choice for all patients with nonthymomatous MG and for selected patients with thymomatous MG. The transthoracic approach is now limited to malignant thymomas and tumors not accessible through the transcervical approach. Formerly, patients coming for thymectomy either already had a preexisting tracheostomy, or an elective tracheostomy was performed at the time of thymectomy. Since 1972, none of these patients has had elective tracheostomy at the time of operation, and only four were performed in the postoperative period, patients being intubated orotracheally at the time of operation. The tube is usually removed within 1 hour after completion of thymectomy. All patients are followed in the intensive care unit for 24 hours or longer, under close supervision of experienced personnel aware of the inherent problems and able to assist ventilation at any stage. This approach has greatly changed the postoperative course of this disease.

Adolescent↗

PubMed1978

Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy.

The idiotype-specific myeloma transplantation resistance induced in BALB/c mice by immunization with the DNP-binding IgAlambda2 protein produced by plasmacytoma MOPC-315 is ablated by post-immunization thymectomy. Sham-thymectomy has no effect. The ablative effect of thymectomy is observed is observed in mice challenged subcutaneously with MOPC-315 cells either 3 days after thymectomy, or after a rest period of 44 days after thymectomy. These observations suggest that short-lived, thymic-dependent suppressive factors may play a role in the idiotype-specific myeloma graft resistance.

Aging↗

PubMed1977

Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice.

NZW F1 (B/W) mice were subjected to sham surgery or neonatal thymectomy and/or splenectomy and studied for immunoglobulin class of antibodies to double-stranded DNA and polyadenylic acid (Poly A) at 4 to 13 months of age. These antibodies occur spontaneously during the course of autoimmune disease in B/W mice. Sera were fractionated by sucrose density gradient ultracentrifugation and assayed for antibodies by a filter radioimmunoassay method. IgM was recovered in the 19S region and IgG in the 7S region as demonstrated by immunodiffusion. In sham-operated controls, at all ages studied, anti-DNA antibodies were both IgM and IgG, with the former predominating in males, and the latter in females. In both sexes, anti-Poly A antibodies were primarily IgM in young mice. There was a sequential switch from IgM to either enhanced or new IgG production in the following sequence: female anti-DNA and anti-Poly A (6 months), male anti-DNA (9 months), and male anti-Poly A (11 months). Both thymectomy and splenectomy caused earlier death in male mice, whereas females lived significantly longer after thymectomy. Neonatal thymectomy in males caused a premature switch from IgM to IgG antibodies to DNA, but it had a transient effect in females. Thymectomy almost completely prevented the late switch to IgG antibodies to Poly A in both sexes. By contrast, splenectomy promoted the formation of IgG antibodies to Poly A in male mice. These results suggest that the newborn B/W thymus and spleen contain regulatory cells and/or factors exerting different controlling influences on spontaneous antibodies to DNA and Poly A. Male B/W mice appear to be under the regulatory influence of suppressor cells, whereas the predominant regulation in female B/W mice appears to be a helper effect.

Age Factors↗

PubMed1977

Contemporary management of myasthenia gravis: the clinical role of thymectomy.

Thirty-six patients with myasthenia gravis have been evaluated and treated over the past five years. Eleven patients had ocular myasthenia gravis and responded well to anticholinesterase medications. Twenty-five patients had generalized myasthenia gravis, and 22 of them were initially treated with anticholinesterase medications; 18(82%) failed to improve or to maintain an initial improvement on medication, and 14 of these 18 patients underwent thymectomy. In addition, 3 patients underwent thymectomy as part of their initial treatment during the later part of this study. All thymectomies were performed through a median sternotomy. All 17 patients manifested sustained improvement as judged by a gain in strength and decrease in medications. Thymectomy is beneficial in the treatment of myasthenia gravis, and it is most efficacious when performed early in the course of the disease.

Adolescent↗

PubMed1976

The value of thymectomy in myasthenia gravis: a computer-assisted matched study.

In the absence of a prospective randomized study of patients treated conservatively or with thymectomy, a computer-assisted retrospective matches study was devised. Of 563 patients treated for myasthenia gravis without thymoma up to 1965, 104 had thymectomy. With computer assistance, each surgical patient was matched with a medical patient on the basis of age, sex, and severity and duration of disease. On this basis 80 of the 104 surgical patients could be matched satisfactorily. There were 16 males and 64 females in each of the matched surgically treated and medical control groups. A complete remission was experienced by 27 of the 78 patients in the surgical group as compared to 6 of the medical group. Improvement was noted by 26 of 78 surgically treated patients and 13 of 78 receiving medical treatment. Survival for patients having thymectomy. Thirty-four patients in the medical group had died as compared to 11 in the surgical group. Comparison of survival in relation to sex, duration of symptoms, or age (less than 30 or less than 30 years) did not show a significant difference. Until more effective treatment is available for myasthenia gravis, thymectomy deserves consideration for both sexes, and with increased age or long duration of symptoms.

Adolescent↗

PubMed1976

Thymectomy for myasthenia gravis.

A group of 71 patients with myasthenia gravis is reviewed. All were initially managed medically, and 18 underwent thymectomy. Twenty-three responded poorly to drug treatment, and seven died from respiratory failure. In contrast, thymectomy was beneficial in 16 of the 18 who were subjected to operation. Seven patients had significant postoperative respiratory complications, and nine required a tracheostomy. Thymectomy appears to be effective and safe and to be indicated in young patients with early disease, and in patients who do not respond to drug treatment. The transcervical approach to thymectomy was satisfactory on two occasions.

Adolescent↗

PubMed1978

Relationships between IgE antibody production and other immune responses. II. Effect of thymectomy at various times after birth.

Mice were subjected to thymectomy at various times after birth and immunized with ovalbumin in aluminum hydroxide gel at 4 or 8 weeks of age. The capacities to produce IgE, IgM and IgG antibodies were abolished by thymectomy carried out within 48 h after birth. The capacity to produce IgE antibody was not affected by thymectomy at 7 days or later, whereas the capacities to produce IgM and IgG antibodies were reduced by thymectomy carried out at 4 weeks of age.

Animals↗

PubMed1976

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↗

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↗

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↗