Neural crest tumour syndromes.

Cells eminating from the embryological neural crest can create different neoplasias, some of them endocrinological active and sometimes multiple (MEN or MEA). The relationship between these conditions and multiple neurofibromas is pointed out. Three cases of MEA which have been operated on at Huddinge Hospital are presented.

Respiratory distress syndrome--a result of disseminated intravascular coagulation (DIC) or of fluid overload.

In 14 patients with the respiratory distress syndrome it was demonstrated that this condition was caused by the administration of excessive volumes of fluid. In none of six patients examined post-mortem were any signs of thrombi or emboli observed in pulmonary vessels. Caution with the initial supply of fluids following major trauma and major surgery is recommended. By monitoring pulmonary arterial pressure, optimum volume replacement with 5% albumin solution for example can be achieved.

Drainage of thoracic duct lymph in renal transplant patients.

Lymphocyte depletion by drainage of lymph via a thoracic duct fistula was accomplished in 51 renal transplant recipients as an adjunct method for immunosuppression. The duration of lymph flow varied between 2 and 53 days and the total drained lymph volume between 1 and 168 liters. The graft survival of these patients was compared to that of a control group of patients undergoing transplantation during a similar period. The followup period was 2-6 years. In patients receiving transplants from living related donors, no beneficial effect of lymphocyte depletion was demonstrated, probably because of the satisfactory graft survival among the control patients (84% at 1 year). However, in recipients of cadaveric kidneys, a significantly higher 1-year graft survival was achieved in the lymph-drained patients. Drainage for more than 30 days and of more than 20 liters improved the results. Additional suppression by thymectomy and institution of antilymphocyte globulin suggested that the best treatment would be a combination of both these measures with lymph drainage continuing for more than 30 days. Infection around the thoracic duct cannula occurred in 5 patients, necessitating removal of the cannula in 2. Two patients developed septicemia. In one of them the infection originated from an infected incisional wound and in the other probably from reinfusion of contaminated lymph plasma. Two other patients developed malignant tumors 23 and 58 months after transplantation, respectively. It is felt that lymphocyte depletion by lymph drainage is an effective supplementary method of immunosuppression to enhance graft survival in recipients of cadaveric renal transplants.

Effects of some immunosuppressive procedures on myasthenia gravis.

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.

Myasthenia gravis: studies on HL-A antigens and lymphocyte subpopulations in patients with myasthenia gravis.

Thirth-three patient with a clinical diagnosis of myasthenia gravis were tissue-typed for HL-A antigens. In agreement with earlier reports a significant increase in antigens HL-A1 and HL-A8 were found in this material. Two of the patients were treated with chronic thoracic duct drainage. Proportions of T and B lymphocytes in lymph and peripheral blood were estimated in these patients. In the lymph an initial decrease in the proportion of T cells occurred, which was accompanied by a subsequent increase in the proportion of B cells. Towards the end of the chronic drainage period this effect was reversed. A slightly different picture occurred in blood lymphocytes. Initially, there was an increase in both T and B cells, followed by a decrease in T-cells numbers in one patient, whereas in the second patient the proportion of T cells decreased from the onset of drainage while the proportion of B cells steadily increased. These studies showed that available markers for determination of T ANd B cells were useful for studies of lymphocyte subpopulations in blood and lymph. Lmyphocytes from the thoracic duct were also tested for their reactivity to various mitogens specific for either T or B cells. The B-cell mitogens which were used were dextran sulphate, lipopolysaccharide, purified protein derivative, as well as rabbit anti-human beta2-microglobulin serum. The T-cell mitogens investigated were concanavalin A and phytohaemagglutinin. No significant differences in the responsiveness of thoracic duct lymphocytes compared to normal peripheral blood lymphocytes were found.

Drainage of thoracic duct lymph in twelve patients with myasthenia gravis.

The effect of thoracic duct lymph drainage (5-34 days) in 12 patients with myasthenia gravis on muscular function has been followed for 5-43 months. Among the results obtained were: (1) During the drainage the myasthenic symptoms decreased markedly after 1-4 days and remained so during the drainage. (2) The doses of cholinesterase inhibitors had to be markedly reduced during the lymph drainage in eight patients. (3) Discontinuation of the lymph drainage increased the myasthenic symptoms within a few days. However, after a median observation time of 14 months with conventional treatment all but one of the patients had improved. (4) Retransfusion of the patients own cell-free lymph caused a worsening of the myasthenic symptoms. This effect could also be obtained following infusion of IgG preparations from the patients lymph. Three retransfusions of cell suspensions obtained from the thoracic duct lymph from two patients had no effects on their myasthenic symptoms. (5) It is suggested that thoracic duct lymph drainage can be combined with other forms of treatment in severe cases of myasthenia gravis.