Defective burst-promoting activity of T lymphocytes from anemic and nonanemic elderly people.

Erythroid stem cell proliferation is regulated by lymphokines and erythropoietin. The helper subset of T lymphocytes is known to produce the erythroid growth factor IL-3 or burst-promoting activity (BPA), while the suppressor subset seems to inhibit the erythroid growth. Leukocyte-conditioned media derived from white cells of nonanemic elderly were reported to provide defective support to the erythropoiesis. In two groups of elderly, nonanemic and anemic, we studied the ability of T lymphocytes to stimulate the BFU-E growth and the in vitro effect of cimetidine, as a drug that inhibits the suppressor T lymphocytes. Culture data were then compared with the peripheral blood lymphocyte picture. The study shows that defective mononuclear cell support to the BFU-E growth, namely due to reduced absolute number of the T4 subset of T lymphocytes, can be observed in both anemic and nonanemic elderly. It is suggested that isolated defective BPA production is not always sufficient to induce anemia. In most cases, anemia of unexplained origin in senescence would be due to the concomitance of both BFU-E impairment and defective BPA production. The simultaneous evaluation of BFU-E growth, lymphokine production, and the T-lymphocyte blood picture offers the best way to investigate the erythropoiesis of the elderly.

Defective in vitro growth of BFU-E of elderly subjects revealed by hydrocortisone.

The effect of aging on hematopoiesis and bone marrow exhaustion have long been debated. Unexplained anemia and impaired in vitro proliferation of erythroid precursors is frequently observed in the elderly. As hydrocortisone is known to increase the BFU-E in vitro growth, we have studied the response of BFU-E to hydrocortisone in a group of nonanemic elderly subjects. The BFU-E growth in methylcellulose from blood mononuclear cells (MNC), stimulated by lymphocyte-conditioned medium (LCM), either with or without hydrocortisone, of 10 subjects aged 76-91 years was compared with the BFU-E growth from MNC of a group of ten young subjects. While LCM induced a significant increase of BFU-E growth, both in young and old subjects, hydrocortisone induced a significant increase of BFU-E growth only in young subjects. This study shows that in the elderly, there is a latent defect of erythropoiesis, possibly consisting of a defective ability to modulate the receptors for erythropoietin on BFU-E, and that hydrocortisone offers a useful tool to identify it.

Effect of cimetidine on burst-promoting activity of normal T lymphocytes.

The effect of cimetidine, an inhibitor of suppressor T lymphocytes, on the burst-promoting activity (BPA) of normal T lymphocytes has been studied. Cimetidine has been shown to increase the BPA of normal T lymphocytes, both when added to the culture and when T lymphocytes were preincubated for 1 h with it. Cimetidine had no direct effect on the in vitro growth of burst-forming units (BFU-E). Our results show that CD8 suppressor T lymphocytes inhibit the in vitro growth of BFU-E in normal conditions, either directly or through inhibition of BPA of CD4 helper T lymphocytes. Cimetidine has proved to be a useful tool for investigating the hematological role of T-lymphocyte subsets in normal and pathological conditions.

Effect of cimetidine on peripheral blood lymphocytes from chronic uremic patients: improvement of burst-promoting activity.

We have studied the in vitro effect of cimetidine, an inhibitor of suppressor T lymphocytes, on T lymphocytes of 6 uremic subjects and on normal T lymphocytes preincubated with the serum from the same patients. Cimetidine has been shown to increase the burst-promoting activity (BPA) of uremic T lymphocytes and to partially improve the BPA of normal T lymphocytes preincubated with uremic serum. The present study shows that suppressor T lymphocytes are not affected by uremic inhibitors and that chronic uremia, besides inducing a decrease in the number of helper T lymphocytes, impairs their ability to stimulate the BFU-E in vitro growth.

In vitro growth of erythroid progenitor cells (BFU-E) and production of burst-promoting activity (BPA) by T lymphocytes in patients with myelodysplastic syndromes.

The in vitro growth of circulating erythroid progenitors (BFU-E) populations and the production of burst-promoting activity (BPA) by T lymphocytes have been studied in 17 patients with myelodysplastic syndromes. Based on the in vitro growth patterns of BFU-E, four groups of patients have been identified: i) normal BFU-E growth; ii) low spontaneous BFU-E growth, but normal response to LCM; iii) impaired BFU-E response to LCM; iv) no BFU-E growth. The pattern of BFU-E growth seems to be related to the clinical stage of the disease rather than to the FAB subgroup to which the patients belong. The ability of T lymphocytes to stimulate BFU-E growth was significantly reduced in all patients. The possible mechanisms inducing the impaired production of BPA by T lymphocytes are discussed. The in vitro evaluation of circulating erythroid precursors can supply useful prognostic information and possibly indications concerning the responsiveness of erythropoietic stem cells to recombinant human erythropoietin in vivo.

T lymphocyte subsets in chronic uremic patients treated with maintenance hemodialysis.

Blood T lymphocyte subsets have been studied using monoclonal antibodies in 10 chronic uremic patients treated with maintenance hemodialysis. Both total T lymphocytes identified by the antibody OKT3, and the helper-inducer T lymphocyte subset identified by the antibody OKT4 were found to be significantly lower than normal. The cytotoxic-suppressor T cell subset was only moderately, even if significantly reduced, so that the T4/T8 ratio in uremic patients was significantly lower than normal. These data provide an additional contribution to the interpretation of immunological and hematological deficiencies observed in chronic uremia.

[Transient loss of consciousness: a frequent and difficult problem in emergency service. Retrospective analysis of 391 cases]. / Perdita transitoria di coscienza: un frequente e difficile problema nel pronto soccorso. Analisi retrospettiva di 391 casi.

The present study was designed to evaluate the patients with transient loss of consciousness who are seen in the emergency room and the ways in which they are currently triaged and evaluated, to determine the risk factors influencing their prognosis, and to analyze the aspects of diagnostic evaluation that are most useful. We made a retrospective study of 391 patients with transient loss of consciousness seen at the emergency room of S. Martino hospital. The causes of loss of consciousness, admission decision, diagnostic tests ordered, initial and final diagnoses and mortality are evaluated. The admission decision was influenced by three factors: cause of loss of consciousness, presence of chronic disease, and patient age. The same factors were shown to influence mortality. Full concordance between initial and final diagnosis was only 50 per cent. In 18.6 per cent of patients the cause of loss of consciousness was not identified at dismissal. The history and physical examination were crucial elements in the evaluation of most patients, and only in selected cases did tests such as electrocardiogram, Holter monitoring, electroencephalogram, computerized tomography scan provide diagnostic information.