Biomedical subjects
Publications and source records attributed to A Tedeschi.
Explore the source record for details and available documents.
A few reports have suggested the beneficial effect of high-dose intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis and cardiomyopathy. We describe a 49-year-old woman in which acute myocarditis was diagnosed on the basis of clinical and echocardiographic findings. Conventional treatment with captopril and frusemide was administered: intravenous heparin and, subsequently, oral anticoagulants were added because of the appearance of an apical thrombus. On the fifth day of hospitalization, treatment with high-dose (400 mg kg(-1) day(-1)) IVIG was started and prosecuted for 5 days. A dramatic improvement of clinical conditions was observed, with increase of the left ventricular ejection fraction (LVEF) from 30% to 75% within 1 week. One year after the diagnosis the patient is in good health, with steady normal LVEF. The rapid recovery, which was immediately subsequent to the administration of high-dose IVIG, suggests that this kind of treatment has been effective in our patient with acute myocarditis.
Mucormycosis infections, caused by fungi of the families Rhizopus, Mucor or Absidia, are typically rapidly progressive and often fatal. We report a 27-year-old male with acute myeloid leukemia (AML) developing an invasive pulmonary-CNS mucormycosis during the neutropenic period after salvage induction chemotherapy; the infection was successfully controlled with surgery and antifungal therapy. The patient received two courses of consolidation chemotherapy and underwent autologous stem cells transplantation (ASCT) while receiving secondary antifungal systemic prophylaxis with liposomal Amphotericin B (L-AMB, Ambisome). There was no clinical, radiological or microbiological evidence of mycotic reactivation during the bone marrow transplantation (BMT) procedure.
Explore the source record for details and available documents.
Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.
Trisomy 12 and deletions of 13q14.2 and 14q32 are the most common chromosome abnormalities in patients with B-chronic lymphocytic leukemia (B-CLL), but whether specific chromosomal defects influence the course of B-CLL is still a matter of discussion. The aim of our study was to assess the possible correlation between cytogenetic findings and clinical characteristics. Thirty patients with previously untreated early-onset B-CLL were recruited. The incidence of trisomy 12, and observations of 13q14.2 and 14q32 was analyzed in unstimulated bone marrow cells by means of multicolor interphase FISH. No correlation was found between trisomy 12 and the patients' clinical characteristics. The analysis of the patients with trisomy 12 and observations of 13q14.2 and 14q32 revealed heterogeneity of the leukemic cell population, thus indicating that these chromosomal abnormalities are probably a secondary event in CLL leukemogenesis. The finding of RB1 gene nullisomy and 14q32 deletions in patients at an advanced clinical stage suggests a possible correlation between these rearrangements and disease progression. Multicolor FISH analysis in B-CLL provides important diagnostic, clinical, and prognostic information that may help in assessing prognosis and making treatment decisions.
Explore the source record for details and available documents.
INTRODUCTION: One hundred-and-six adult cases of acute lymphoblastic leukemia were prospectively investigated using a highly sensitive interphase fluorescence in situ hybridization assay which utilizes DNA probes that detect a double BCR/ABL fusion signal (D-FISH) in cells carrying the t(9;22) to evaluate the reliability and specificity of this method for the detection of the Ph translocation. The results were compared with those obtained in the same cases by conventional cytogenetics and by reverse-transcription polymerase chain reaction. MATERIALS AND METHODS: The study was performed using DNA probes that span the common breakpoints of the t(9;22) translocation and that detect a double BCR/ABL fusion in cells carrying this karyotypic anomaly, one on the abnormal chromosome 9 and one on the Ph chromosome. RESULTS: Interphase D-FISH detected a high number of rearranged cases (22/106) compared to conventional cytogenetics (15/106) and RT-PCR (21/106). CONCLUSION: Interphase D-FISH emerges as a reliable, fast and relatively inexpensive tool for the detection of BCR/ABL rearrangements in adult ALL patients at diagnosis. It has a sensitivity clearly higher than conventional karyotyping and it may prove also superior to that of RT-PCR in cases with unusual BCR/ABL breakpoints. Our results suggest that D-FISH might be considered as the initial test for the diagnosis of Ph+ adult ALL.
BACKGROUND: Recently, distinct studies have shown that: (a) chronic idiopathic urticaria (CIU) is autoimmune in 30-50% of cases; (b) in patients with CIU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement-dependent. OBJECTIVE: To carry out a comprehensive clinical and serological study on CIU based upon these observations. METHODS: Three hundred and six adults with CIU underwent intradermal (ID) test with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in vitro histamine release from basophils of normal donors. The effects of heating (56 degrees C, 60 min), filtration through membrane, and preincubation with heparin were evaluated as well. RESULTS: Autologous serum and plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Positive plasma skin tests were observed only in patients showing strongly positive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patients with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release from basophils of normal donors. 19/20 sera were from patients with a positive intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 degrees C x 1 h markedly reduced the histamine-releasing activity of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine-releasing activity, whereas fractions < 100 kDa were not able to induce any histamine release. Heparin dose-dependently inhibited histamine release induced by sera and plasma, and by basophil agonists such as anti-IgE, formyl-methionyl-leucyl-phenilalanine, and interleukin (IL)-3. CONCLUSIONS: 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked difference between in vivo and in vitro findings could reflect the existence of a mast cell-specific histamine-releasing factor which does not release histamine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil donors. At least in some cases complement seems essential for histamine-releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (in vivo), probably acting directly at a cellular level.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder characterised by intermittent, diffuse alveolar hemorrhage (DAH). Although an inflammatory pulmonary capillaritis can be evidenced in most patients with DAH, IPH is a distinct entity in which pulmonary inflammatory alterations are lacking. Most cases occur in children, although the disease has been exceptionally reported in adults too. Here, we, describe a case of IPH in a 30-year-old woman who was admitted to our hospital because of recurrent episodes of hemoptysis since the age of 21. IPH was diagnosed on the basis of: 1) an open lung biopsy showing focal alveolar edema and hemorrhage without parenchymal inflammatory alterations, 2) a bronchoalveolar lavage showing hemosiderin-laden macrophages, and 3) exclusion of infectious or immunologic causes of hemoptysis. Prednisone administration could control the disease, but every attempt to lower the dose to less than 25 mg per day was followed by recurrence of hemoptysis. Then, azathioprine was started, and after three months prednisone was gradually tapered to the dose of 10 mg per day, without any relapse of the disease. These findings indicate that azathioprine, in combination with prednisone, may be an effective therapy for IPH and suggest that an immunologic mechanism could be involved in the pulmonary capillary damage underlying alveolar bleeding.
Explore the source record for details and available documents.
OBJECTIVE AND DESIGN: This study was aimed to evaluate the effects of two protein kinase C (PKC) inhibitors (staurosporine and chelerythrine) and one phospholipase C (PLC) inhibitor (U73122) on basophil histamine release induced by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), IL-3 and GM-CSF. METHODS: Leukocytes were suspended in solutions containing physiological or low Na+ concentrations, since IL-3 and GM-CSF were shown to induce histamine release only when the inhibitory effect of extracellular Na+ has been removed. After incubation with PKC and PLC inhibitors, the stimuli were added and histamine release was measured by an automated fluorometric method. RESULTS: Staurosporine and chelerythrine exerted a significant inhibitory effect on histamine release induced by anti-IgE, IL-3 and GM-CSF at concentrations much higher than those required to inhibit PKC. FMLP-induced histamine release in a physiological Na+-containing medium was not significantly modified by staurosporine, although it was reduced by high concentrations of chelerythrine. A slight inhibition by high concentrations of staurosporine was found when basophils were suspended in a low Na+ medium. U73122 exerted a significant and dose-dependent inhibitory effect on basophil histamine release induced by anti-IgE, FMLP, IL-3 and GM-CSF. CONCLUSION: These results suggest that a prodegranulatory role of PKC in basophil histamine release induced by anti-IgE, FMLP, IL-3 and GM-CSF is unlikely; conversely, it is conceivable that PLC has a role in signal transduction and histamine release induced by the above stimuli.
It has been demonstrated that tyrosine kinase (TK) and phosphatidylinositol 3-kinase (PI3-K) are involved in IgE-mediated stimulation of human basophils; conversely, little is known about the biochemical pathways activated by IL-3 and GM-CSF. The aim of this study was to evaluate the effects of TK and PI3-K inhibitors on basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. Since IL-3 and GM-CSF cause histamine release from normal human basophils only when the inhibitory effect of extracellular Na(+) has been removed, peripheral blood leukocytes were suspended in isotonic solutions containing either 140 mM NaCl or 140 mM N-methyl-D-glucamine(+). After stimulation with anti-IgE, IL-3 or GM-CSF, histamine release was measured by an automated fluorometric method. The effects of preincubation with four different TK inhibitors (AG-126, genistein, lavendustin A, tyrphostin 51) and one PI3-K inhibitor (wortmannin) were evaluated. AG-126, genistein and lavendustin A exerted a significant dose-dependent inhibitory effect on basophil histamine release induced by anti-IgE (either in high or in low Na(+) medium), IL-3 and GM-CSF. Among the TK inhibitors, lavendustin A exerted the most potent activity, followed by AG-126 and genistein. Tyrphostin 51 caused a weak inhibition of histamine release induced by IL-3, GM-CSF and anti-IgE in a low Na(+) medium, but not in a physiological Na(+)-containing medium. The PI3-K inhibitor wortmannin exerted the most effective inhibitory activity on the histamine release induced by the three agonists. The combined effects of lavendustin A and wortmannin were less than additive, suggesting that TK and PI3-K are involved in the same activation pathway in human basophils. These results suggest a possible role of TK and PI3-K in basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. TK and PI3-K are indeed potential therapeutic targets for antiallergic drugs.
Explore the source record for details and available documents.
The present study was undertaken to evaluate the efficacy of the association of fludarabine plus Ara-C and G-CSF (FLAG) in the treatment of 15 patients with chronic myeloid leukemia in the blastic phase (CML-BP). Patients achieving a partial remission (PR) after the first course received a second FLAG. Complete remission (CR) was consolidated with another FLAG regimen. Patients were then submitted to an individualized program of treatment depending on age and suitable donors. Overall seven patients achieved CR (46.7%), three (20%) showed a primary resistant disease, while three (20%) died during remission induction therapy. Five of them received a consolidation therapy; in two cases further treatment was not performed because of severe toxicity. Median overall survival and disease-free survival were of 7.5 and 4.5 months, respectively. FLAG proved to be effective in achieving a high CR rate in patients with CML-BP. Median overall survival and disease-free survival were not significantly improved compared to previous studies. Nevertheless, the treatment was well tolerated even in a group of heavily pretreated patients, allowing further transplantation opportunities in younger patients.
Elderly patients with untreated acute myeloid leukaemia (AML, n = 47) tested the feasibility of out-patient consolidation therapy and post-consolidation treatment (for patients aged < 71 years) with autologous peripheral blood stem cell transplantation (APBSCT). Overall, 13 patients out of 24 (51%) who achieved complete remission (CR) were eligible for further treatment after consolidation. Five patients were primed with granulocyte colony stimulating factor (G-CSF); a suitable number of CD34+ cells were harvested in three patients and were actually autotransplanted. The toxicity of APBSCT was negligible. Psychosocial problems impaired treatment of some patients on an out-patient basis. Resistant disease, toxicity and logistic problems reduced the number of patients to whom this procedure could actually be applied.