Biomedical subjects
Publications and source records attributed to R L Sewell.
A case of adult Fanconi syndrome is described in which there was urinary excretion of kappa light chains. After 13 years the patient developed overt myeloma. She also developed an adenocarcinoma of the colon and an adenocarcinoma of the parathyroid gland. These findings are discussed in relation to the known association between adult Fanconi syndrome, renal damage, and myeloma.
Lymphopenia and monocytosis were found in one third of untreated myeloma patients but there was no correlation between the two. Half of the patients studied had an increase in medium basophilic lymphoid cells, and eight had a raised PAS score. Lymphocytes from the majority of untreated myeloma patients failed to respond to antigenic stimulation in vitro compared with age matched controls. Three patients were immunized but showed no increase in immunoblasts or rise in antibody titre. The findings strongly suggest that abnormal lymphocytes are present in the blood in myeloma. The failure of lymphocytes to respond to antigen provides an explanation for the lack of normal plasma cells and depressed antibody responses in myeloma.
A study of the thymidine labelling index (TLI) of bone marrow blast cells in 58 untreated patients with acute myelogenous leukemia showed no correlation with remission rate but there was a strong correlation between labelling index and remission length in the 21 patients who achieved remission. The median remission length of the patients was 33 weeks. Of the 12 patients with initial labelling indices greater than 10%, only 2 had remissions longer than 33 weeks whereas 8 of the 9 patients with labelling indices less than 10% had remissions longer than 33 weeks. No correlation could be found between the degree of cytological differentiation and remission induction, remission length or survival. No correlation was found between the TLI and the degree of cytological differentiation. Age and initial platelet count were confirmed to be important factors influencing complete remission rate, but these factors did not correlate with remission length. Sixteen patients had their pretreatment sera assayed for mouse marrow colony stimulating activity and inhibitor levels but there was no correlation with subsequent response to treatment, although the number of patients examined was clearly too small for any definite conclusions to be drawn.
Reactive changes in the lymphoid cells are seen in patients with active rheumatoid arthritis and the degree of reactivity is related to the activity of the disease. The test may be useful as an early indication of relapse in autoimmune disease. Changes are also described in the lymphoid cells of the blood in patients with idiopathic thrombocytopenic purpura, which are identical with those seen in other autoimmune disorders, in infections, and following immunization. This provides supporting evidence for the autoimmune nature of this disease. In contrast with this, patients with aplastic anaemia have been found to have entirely normal lymphoid cell populations in the peripheral blood and provide no evidence that this condition has an autoimmune basis.
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The lymphoid cell population in the peripheral blood in Hodgkin's disease differs from normal blood in three ways. Firstly, the number of large lymphoid cells actively synthesizing deoxyribonucleic acid is increased; secondly, the number of medium-sized lymphoid cells with intensely basophilic cytoplasm is increased; and, thirdly, occasional plasma cells are seen. These changes are related to the activity but not to the stage of the disease.Similar changes are found under conditions of known antigenic challenge-that is, in infections, and after immunization, and in rheumatoid arthritis and systemic lupus erythematosus.
A combined morphological and metabolic study has been made of the lymphoid cells in the blood during the immune response in man. Similar changes were observed in both primary and secondary responses to a number of different microbial antigens. The cellular response involved an increase in numbers of three types of cell; hyperbasophilic medium lymphocytes, plasma cells, and large lymphoid cells. The large lymphoid cells were about 20 micro in diameter with large nuclei, prominent nucleoli, and an intensely basophilic cytoplasm with numerous polyribosomes. About 30% of these cells were in the DNA synthetic phase of cell growth. Electron microscopy has shown that many of the basophilic medium-sized cells have sufficient well-organized endoplasmic reticulum to be included in the plasma cell series. The hyperbasophilic cells labeled more heavily with tritiated uridine and tritiated leucine than the normal small and medium lymphocytes from the peripheral blood of patients not under antigenic stimulation. The evidence in this paper supports the argument that the atypical mononuclear cells first described by Türk and others in the blood of patients with infections are immunoblasts, plasma cells, and other reactive lymphoid cells representing a circulating population of lymphoid cells derived from lymphoid tissue responding to antigenic stimulation. The presence of such cells may be a valuable indication that an immunological reaction is in progress when direct proof is lacking.
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