Plasma exchange alone as therapy for myasthenia gravis.
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Biomedical subjects
Publications and source records attributed to W Ho.
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In the isolated dog ileum perfused with constant flow, nitroglycerin (NTG) produced dose-dependent arteriolar and venous dilatation. Experiments were performed in 22 ileum preparations to advance the study on the pre- and postcapillary resistances, functional capillary pressure, capillary filtration coefficient (CFC) and vascular compliance. At venous pressure (Pv) of 0, 10 and 20 mm Hg, and intra-arterial infusion of NTG in a submaximal dose (30 microgram/min) reduced the total and precapillary resistances, but did not change the postcapillary resistance and functional capillary pressure. This agent slightly increased the CFC calculated from a Pv range of 0 to 10 mm Hg and significantly increased the CFC value calculated from a Pv change of 0 to 20 mm Hg. At Pv = 0 mm Hg, NTG infusion caused a regional volume pooling by 1.2 +/- 0.4 mg/100 g. The vascular compliance in terms of delta blood volume/delta Pv was also significantly increased after NTG. The myogenic responses (reduction in CFC and increase in precapillary resistance) to an elevation of Pv were essentially identical before and after NTG infusion. The results suggest the NTG at the dose used acts primarily on the arterioles, precapillary sphincters and postcapillary capacitance vessels. The postcapillary resistance vessels (mainly the venules) are little affected. Although the resistance and exchange vessels are dilated by NTG, the myogenic constriction of these vessels upon Pv rises is not significantly altered.
Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.
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We studied the role of ABH antigens in determining graft outcome in 104 patients who received HLA-identical bone marrow transplants for aplastic anaemia and acute leukaemia. ABH compatibility had no significant effect on incidence of graft rejection or graft-versus-host disease. Fifteen recipients ahd pre-transplant antibodies against donor ABH antigens. In 14, large volume plasma exchange and transfusion of donor-type erythrocytes was successful in reducing the antibody titre to low or undetectable levels. In one patient, plasma exchange was unsuccessful and red cells were removed from the marrow inoculum by unit gravity sedimentation. This approach prevented transfusion reaction, and permitted engraftment of all haematopoietic cell lines despite persistently elevated antibody titres. Parallel in vitro studies revealed that antibodies to ABH antigens failed to inhibit the growth of progenitor cells committed to both granulocyte-macrophage (CFU-C) and erythroid (BFU-E) development. These findings indicate that ABH-antigens are not clinically important transplantation antigens and suggest that ABH antigens are not operationally present on hematopoietic stem cells.
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Ten patients with non-leukemic neoplasms received intensive, marrow-lethal doses of drugs and radiation followed by rescue with autologous cryopreserved bone marrow (nine) or marrow from an identical twin as part of a phase 1-2 study. Nine patients had extensive disease that was unresponsive to conventional therapy. Marrow engraftment was documented in all evaluable cases and most patients had a substantial anti-tumor response. Three patients are alive from 4 to 10 months following transplantation without evidence of disease.
A specific inhibitor of fatty acid oxidation, methyl 2-tetradecylglycidate (McN-3716) has been found to produce a dose dependent hypoglycemic effect when administered orally to rats, mice, and dogs. In addition to being more potent than other inhibitors of fatty acid oxidation, McN-3716 was also found to be 15--20 times more potent than tolbutamide in lowering the blood glucose of fasting rats. Furthermore, evidence is presented that McN-3716 produces hypoglycemia by a mechanism which differs from that of other oral hypoglycemic agents, the biguanides and the sulfonylureas. As predicted by the Randle glucose-fatty acid cycle, McN-3716 lowered glucose concentrations only under conditions where fatty acids were being used as the major energy substrates (fasting, diabetes, and feeding of high fat diets) but not under conditions where energy was derived mainly from carbohydrate (fed state or following hypophysectomy). Administration of McN-3716 produced a remarkable lowering of the plasma glucose and the glycosuria of depancreatized dogs but did not result in complete normalization of glucose, especially the excursions of blood glucose following feeding. It did, however, produce virtually complete reversal of the ketoacidosis of alloxan diabetic rats and depancreatized dogs without worsening the plasma lipid profile. Thus, McN-3716 may have potential utility as an oral therapeutic agent for the treatment of ketosis-prone juvenile or maturity-onset diabetes.
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The role of the ABO blood group system in determining the outcome of bone marrow transplantation was investigated in 53 patients with aplastic anemia and acute leukemia grafted from HLA-identical siblings. There was no correlation between ABO compatibility and marrow engraftment, graft rejection, or graft-versus-host disease. In 5 recipients with antibodies prior to transplantation to antigens of the ABH system present on the cells of their donors, plasma exchange and antibody absorption in vivo were effective in permitting engraftment of ABO-incompatible bone marrow. These findings indicate that the ABO system is not a clinically significant barrier to successful bone marrow transplantation in otherwise histocompatible individuals.
Fibrinogen labeled with iodine 125 was used to detect deep vein thrombosis (DVT) in 35 patients during their course and convalescence from acute myocardial infarction. Clinical status was assessed and scored with the use of a modified coronary prognostic index. According to the prognostic scores, patients were allocated to one of two groups. Of 27 patients in good clinical condition, DVT developed in only one patient, whereas thromboembolic complications occurred in seven of eight patients who were severely ill--a highly significant difference. Prophylactic anticoagulation is advisable in patients at risk.
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Epidural myeloblastoma, which compressed the spinal cord, was the first evidence for chronic granulocytic leukemia, eosinophilic type, Ph chromosome negative. This manifestation was preceded by 3 years follow-up of a patient with persistent eosinophilia of 60% mature eosinophils. The only clues for the diagnosis of leukemia were splenomegaly and high serum vitamin B12, most of which was bound to transcobalamin I. The latter finding presents a useful diagnostic criterium in myeloproliferative disorders.
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