Interferon retreatment in chronic hepatitis C: which patients to choose, and what schedule to use.

UNLABELLED: OBJECTIVE; To evaluate the results of a large cohort of non-responder or relapsing responder patients with chronic hepatitis C retreated with various schedules of interferon (IFN). METHODS: Our study included 276 patients (158 non-responders and 118 relapsing responders) who underwent IFN retreatments. Among the non-responder group, 158 patients underwent further courses of IFN. In particular, 108 patients underwent one course of IFN retreatment, 40 patients underwent two courses, eight patients underwent three courses, and two patients underwent four courses. Regarding the relapsing responder group, the 118 patients were retreated with the same dosage for varying periods. In particular, 50 patients were treated for 6 months, 43 patients for 12 months, and 25 for 24 months. Patients in the subgroups of IFN retreatment were homogeneous as far as age and gender distribution, as well as virological and histological characteristics, are concerned. Qualitative and quantitative HCV-RNA was evaluated at baseline, at the end of treatment and at the last check-up of follow-up. HCV genotype was determined on baseline serum samples. Alanine transaminase (ALT) levels were tested monthly. RESULTS: Long-term biochemical (normal ALT levels) and virological (HCV-RNA negative) response was obtained in 2.6% of non-responder retreated patients, and in 33.9% of relapsing responder retreated patients. Evaluation of response on the basis of the duration of treatment showed that 48%, 19% and 16% of relapsing responder patients retreated for 24, 12 and 6 months, respectively, obtained long-term biochemical and virological response. CONCLUSION: Non-responder patient retreatment is inefficient especially in cirrhotic and/or genotype 1 b patients. IFN retreatment is warranted in relapsing responder patients. In particular, 24-month therapy induces significant long-term biochemical and virological response.

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.

[Therapy of chronic non-A, non-B hepatitis with interferon alfa-2B. A controlled clinical study and long-term follow-up]. / Terapia dell'epatite cronica non-A non-B con alfa-2b interferone. Studio clinico controllato e follow-up a lungo termine.

In order to assess the efficacy of alpha-2b interferon (r-IFN) in the treatment of non-A non-B chronic hepatitis, 30 patients were randomised to receive r-IFN (3 MU subcutaneously three times a week for 24 weeks) or no therapy. A total of 21 males and 9 females, aged between 24-66 years old and who had had increased transaminase levels for at least one year, were included in the study. Three patients were ex-drug addicts and 6 had received blood transfusions whereas the cause of the infection in the remaining 21 patients was unknown. Hepatic biopsies performed prior to the study revealed persistent chronic hepatitis in 7 patients, active chronic hepatitis (ACH) in 19 patients and ACH with hepatic cirrhosis in 4 patients. Anti-HCV antibodies were present in 21 patients (70%). Transaminase values returned to normal in 11 (73%) of the 15 patients treated and remained unchanged in controls after 6 months of therapy. During the 18-month follow-up following the suspension of r-IFN treatment, transaminase values rose again to pre-treatment levels in 4 patients. Anti-HCV antibodies did not disappear in any of the patients who responded to therapy.

[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.

Effect of hydrocortisone on BFU-E growth and on burst-promoting activity of T lymphocytes in man.

Glucocorticosteroid hormones have been reported either to stimulate or to inhibit human erythropoiesis. We have studied the in vitro effect of hydrocortisone, 10(-6) mol/l, on human BFU-E when stimulated by preconstituted burst-promoting activity (BPA) in a medium conditioned by T lymphocytes. Hydrocortisone was found to stimulate BFU-E growth, even at largely suboptimal concentrations of BPA, through hormone receptors, as the effect was blocked by preincubation of BFU-E with equimolar progesterone. The possibility that glucocorticosteroids may increase the number and/or affinity of erythropoietin receptors on BFU-E is discussed. We have also studied the effect of hydrocortisone on the production of BPA by human T lymphocytes stimulated by phytohemagglutinin. Preincubation of T lymphocytes for 1 h with hydrocortisone, 10(-6) mol/l, significantly reduced the BPA of lymphocyte-conditioned medium. Again the inhibition of BPA production was reversed by incubation of lymphocytes with equimolar doses of progesterone. The conflicting results previously reported on the effect of glucocorticosteroids on erythropoiesis may be due in part to the opposing effects of the hormones on BFU-E growth and BPA production. The role hydrocortisone plays in the physiological regulation of human erythropoiesis is at present largely unknown.