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Biomedical subjects

M Picardi

Publications and source records attributed to M Picardi.

At least 19 recordsLinked to original sources

Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients with hematologic malignancies developing a filamentous fungi infection (FFI) and to define the prognostic factors for their outcome. DESIGN AND METHODS: A retrospective study, conducted on patients admitted to 14 Hematology divisions of tertiary care or university hospitals, participating in the GIMEMA Infection Program, over a ten-year period (1988-1997). The study included patients with hematological malignancies and a histologically and/or microbiologically proven or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12 myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who developed a proven FFI. Eighty percent of the patients had been neutropenic for an average of 14 days before the infection, and 71% had an absolute neutrophil count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of infection were: lungs (85%), nose and paranasal sinus (10%), and other sites (5%). The diagnosis was made while still alive in 310 patients (79%), and at autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of patients with pulmonary FFI, while computed tomography (CT) scan of the thorax was positive in 95% of cases. A significant diagnostic advantage for CT scan was observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was identified as the cause of FFI in 296 patients, Mucorales in 45 patients, Fusarium in 6 patients and other filamentous fungi species in 4 patients, while in a further 40 patients no agent was identifiable. The overall mortality rate three months after the diagnosis of FFI was 74%, and fungal infection had been the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our retrospective study shows that FFI still remains a life-threatening complication in neutropenic patients. Despite appropriate treatment, half of the patients die due to this complication. The use of glucocorticoids and recovery from neutropenia are the most important prognostic factors. Mucorales infections are associated with a significantly poorer prognosis than those due to Aspergillus spp.

Adolescent↗

Thrombocytopenia and purpura-like lesions associated with clopidogrel.

We report a case of moderate thrombocytopenia associated with purpura-like phenomenon (four ecchymoses) that occurred within 72 hours of clopidogrel initiation and resolved promptly with drug withdrawal. This 61-year-old patient previously experienced an adverse skin reaction to ticlopidine without changes in the platelet count and without any other laboratory abnormalities. Since the introduction of clopidogrel instead of ticlopidine for the prevention or treatment of several cardiovascular diseases, only 11 cases of thrombotic thrombocytopenic purpura among more than 3 million individuals treated with clopidogrel have been reported. Recently, a case of severe thrombocytopenia, without concomitant purpura-like lesions, during therapy with clopidogrel has been described. To our knowledge, this is the first case of thrombocytopenia associated with purpura-like lesions with no evidence of thrombotic thrombocytopenic purpura during clopidogrel treatment.

Clopidogrel↗

Long-lasting decrease of marrow and circulating long-term culture initiating cells after allogeneic bone marrow transplant.

We investigated bone marrow (BM) and circulating (PB) hematopoietic progenitor cells in 37 normal donors and in 25 patients 1 to 8 years after successful allogeneic bone marrow transplant. At the time of testing, transplanted patients had normal blood counts and bone marrow cellularity. By flow cytometry, BM CD34+ cells were found to be three- to four-fold decreased in transplanted patients compared to normal donors, while the number of PB CD34+ cells was the same as in normal donors. Using a methylcellulose colony assay, primary BM colony-forming cells (CFU-GM) were decreased 2.1-fold, whereas PB CFU-GM were only marginally decreased. In a long-term culture initiating cell (LTC-IC) assay, an eight-fold decrease of early progenitor cells was observed in the marrow of transplanted patients compared to normal donors, and a five-fold decrease was documented in peripheral blood. We found that the BM LTC-IC cell number correlated with concurrently determined BM CD34+ cells and committed progenitor cell number (measured as CFU-GM) and with PB LTC-IC number, but not with PB CFU-GM and CD34+ cells. We conclude that marrow and circulating early stem cell compartments, as measured by the LTC-IC assay, are greatly and permanently depressed following bone marrow transplant. The correlation between BM and PB LTC-IC indicates that the enumeration of circulating LTC-IC can be used as a measure of the stem cell compartment in the bone marrow after transplant. It seems that the deficiency of the most immature progenitor cells persists forever after successful bone marrow transplant; this means that a complete hematopoietic reconstitution can be sustained by a reduced stem cell pool.

Adolescent↗

Spleen sizing by ultrasound scan and risk of pneumococcal infection in patients with chronic GVHD: preliminary observations.

Encapsulated bacteria infections (EBI) can cause severe complications after BMT, usually occurring in patients with chronic GVHD (cGVHD) and attributed to functional hyposplenism. Using ultrasound (US) scan, we measured spleen size in 22 patients transplanted from HLA identical siblings, with or without cGVHD. No patient had received TBI, spleen irradiation or penicillin prophylaxis. Results were correlated with occurrence of EBI during a mean follow-up of 55 months (range 7-93). In the group without cGVHD, the difference between pre- and post-BMT spleen longitudinal diameters was not significant, and no patient developed EBI. In the cGVHD group, post-BMT spleen longitudinal diameters were significantly smaller than those pre-BMT (9.1+/-1.6 vs. 12.3+/-2.2; P = 0.0005). Out of four patients with cGVHD who showed a major spleen size reduction, two developed a severe infection (an overwhelming sepsis and a pneumococcal meningitis). In our small series, we found a borderline relationship between spleen size reduction and duration of cGVHD (P = 0.06), as well as an increased risk of life-threatening infection in patients with extensive cGVHD and hyposplenism as detected by US scan. We conclude that US scan may be useful to detect spleen size reduction following allogeneic BMT and that penicillin prophylaxis is to be strongly recommended in patients with extensive cGVHD and spleen size reduction, even in those who have not received total body or spleen irradiation.

Adult↗

Early detection by ultrasound scan of severe post-chemotherapy gut complications in patients with acute leukemia.

BACKGROUND AND OBJECTIVE: Acute leukemia patients may develop life-threatening gut complications after intensive chemotherapy. We evaluated the role of abdominal and pelvic ultrasound (US) examination in early detection of these complications. DESIGN AND METHODS: A cohort of twenty adult acute leukemia patients undergoing intensive chemotherapy for remission induction entered the study. All chemotherapy regimens included cytarabine by continuous i.v. infusion for several days. RESULTS: Three patients had severe gut complications: 2 cases of enterocolitis and 1 case of gall bladder overdistension in the absence of calculi. In all cases the abnormality was documented by US examination: US scan showed thickening of the intestinal wall (two cases), and gall bladder overdistension with biliary sludge (one case). Immediate medical care included bowel rest, a broad-spectrum antibiotic, antimycotic treatment, and granulocyte colony-stimulating factor. All patients recovered from the complication. INTERPRETATION AND CONCLUSIONS: We believe that the favorable outcome obtained in our small series can be attributed to early diagnosis followed by appropriate treatment. Early recognition by US and immediate medical management can lead to complete recovery of severe intestinal complications in patients with acute leukemia undergoing intensive chemotherapy.

Acute Disease↗

Lamivudine treatment for chronic replicative hepatitis B virus infection after allogeneic bone marrow transplantation.

The risk of severe hepatic damage in patients with chronic hepatitis B virus (HBV) infection is well known; more effective treatments for this infection are needed. Lamivudine is being studied in immunocompetent and immunosuppressed HBV infected patients. We report a patient suffering from chronic replicative HBV infection after allogeneic BMT, who responded to lamivudine therapy. A 24-year-old woman with CML received an allogeneic BMT from her HLA-identical sister in June 1992. Before transplant, her HBV status demonstrated viral contact without active infection (HBsAb+, HBcAb+ IgG, HBeAb+). Four months after BMT mild chronic liver GVHD appeared, requiring immunosuppressive treatment. Antibodies to HBV completely disappeared post-transplant. Acute icteric hepatitis occurred 2 years later, with HBsAg+, high level of HBV-DNA, HBeAg+ and HBcAb IgM+. Lamivudine 100 mg/day rapidly reduced transaminase levels and effected HBV-DNA disappearance within 2 months. The treatment was well tolerated; no hematological side-effects occurred. This preliminary observation warrants further investigation of lamivudine treatment in bone marrow transplanted patients with active HBV infection.

Adult↗

CD34+-enriched donor lymphocyte infusions in a case of pure red cell aplasia and late graft failure after major ABO-incompatible bone marrow transplantation.

A variety of immunohematological complications may occur after ABO-incompatible BMT. We report a CML patient (blood group O) who received a BMT from an HLA-identical sibling (blood group AB). The transplant was followed by normal myeloid and megakaryocytic engraftment, but erythroblastopenia persisted for more than 200 days after BMT. By bone marrow culture studies, a complement-dependent serum inhibitor of hemopoiesis was detected, suggesting immunological inhibition of erythropoiesis. The patient was resistant to a number of treatments such as intravenous gamma-globulins, prednisolone and high-dose erythropoietin. Full engraftment with normal blood counts and marrow cellularity was achieved after two dose-escalating CD34+-enriched donor lymphocyte infusions (DLI). This experience suggests that CD34+-enriched DLI may be an effective treatment for patients with delayed engraftment or late graft failure due to major ABO-incompatibility.

ABO Blood-Group System↗

Ultrasound-guided fine needle cutting biopsy for the characterization of diffuse liver diseases in bone marrow transplant patients.

Liver disease is a frequent complication in bone marrow transplant recipients and may occur early or late in the post-transplant period. Using ultrasound-guided fine needle (1.2 mm, 18 G) cutting biopsy, we studied six patients with undefined late post-BMT liver disease. No procedure-related complications occurred and all liver biopsies were informative, leading to changes in therapeutic approach. In our small series, the most frequent cause of hepatic damage was drug toxicity. US-guided fine needle cutting biopsy is a useful and easy tool for the work-up of unexplained post-BMT liver disease.

Adolescent↗

Post-transplant cerebral toxoplasmosis diagnosed by magnetic resonance imaging.

Cerebral toxoplasmosis is a rare late complication in allogeneic bone marrow transplanted patients. Neuroradiological findings may suggest the correct diagnosis. We report a patient in whom cerebral magnetic resonance imaging (MRI) showed a lesion characteristic of toxoplasmosis. Anti-toxoplasma treatment led to clinical and radiological improvement. MRI seems to be a valid tool for detection and follow-up of cerebral toxoplasmosis.

Adult↗

High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy.

Starting from the observation that a number of consecutive patients with non-Hodgkin's lymphoma (NHL) resulted positive for hepatitis C virus (HCV) antibodies on routine testing, we set up a survey for HCV contact prevalence in all patients with lymphoproliferative disorders (LPD) followed in our institution. We searched for HCV antibodies by a third-generation ELISA technique, followed by a confirmation test (RIBA III); serum viral RNA and HCV genotype were investigated by a RT-PCR technique. We screened a total of 315 patients suffering from B-NHL (91), multiple myeloma (56), MGUS (48), chronic lymphocytic leukemia (57), Waldentrom's macroglobulinemia (13), Hodgkin's disease (HD)(43), and T-NHL (9). While only 1 of 52 patients with a non-B-LPD (HD or T-NHL) had signs of HCV contact (i.e., 1.9%, which is in the range of the normal population in the South of Italy), 59 of 263 patients with a B-LPD (22.4%) had HCV antibodies or RNA, or both, with no major differences among the various types of disorders, except for WM, in which the rate was higher (61.5%). The same prevalence was found for patients tested at diagnosis or during the follow-up, and in transfused or never-transfused patients. Only a few patients were aware of having a liver disease; one-half of HCV-positive patients never had transaminase increase. A review of data from Central and Northern Italy is included, showing similar findings; a report from Japan has confirmed such an association, while limited surveys in England have not revealed any correlation. These findings may have important biological and clinical implications.

Adolescent↗

Combined treatment with amphotericin-B and granulocyte transfusion from G-CSF-stimulated donors in an aplastic patient with invasive aspergillosis undergoing bone marrow transplantation.

Granulocyte transfusions from G-CSF stimulated donors were added to standard anti-infective treatment in preparation for and during allogeneic bone marrow transplantation in a young man affected by very severe acute aplastic anemia and invasive aspergillosis. Nine concentrates with a mean neutrophil content of 18.7 x 10(9)/L (2.6 x 10(8)/kg patient b.w.) were transfused before and after marrow infusion. An impressive clinical improvement was noticed after each granulocyte transfusion, although this was not always paralleled by a neutrophil increase in the peripheral blood. Engraftment (N > 0.5 x 10(9)/L and Plt > 25 x 10(9)/L) was verified at +16 and +40 days, respectively. The patient is currently in complete hematological and microbiological remission 14 months after transplantation. Granulocyte apheresis from G-CSF stimulated donors provides a high number of activated neutrophils. At the dose given (300 micrograms/day) donor tolerance to G-CSF was excellent. This new approach is indicated when life-threatening infections develop in patients exposed to prolonged severe neutropenia.

Acyclovir↗