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Biomedical subjects

P Macchia

Publications and source records attributed to P Macchia.

At least 19 recordsLinked to original sources
PubMed2004

Horse antilymphocytic globulin in hepatitis B exacerbation after bone marrow transplantation adoptive immunity transfer.

We describe the case of a HBsAg+, HBeAg+ carrier, treated with lamivudine, who experienced exacerbation of hepatitis after BMT from an anti-HBs+, anti-HBc+, anti-HBe+ donor. The serological profile of the donor and the timing of exacerbation suggested that the adoptive immunity transfer played a major pathogenetic role. Antilymphocyte globulin administration resulted in resolution of hepatitis and seroconversion to anti-HBs+. Therapy aimed at blocking the effector arm of liver damage could represent a novel approach to avoid the risk of progression to fulminant hepatitis without hampering the chances of recovery from hepatitis B.

Adoptive Transfer↗
PubMed2004

"Cyst-like" structures within the ciliary shafts in children with bronchiectasis.

"Cyst-like" structures within the ciliary shafts were considered in four adults as a primary defect involved in the development of bronchiectasis. In this study, the presence and the primary or secondary nature of this abnormality were assessed in children with bronchiectasis. High resolution computed tomography (HRCT) and nasal biopsies for motion analysis and transmission electron microscopy (TEM) evaluation of cilia were obtained in 45 children with recurrent lower airway infections and abnormal chest radiography. HRCT disclosed bronchiectasis in 35 out of 45 (77.8%) children and cyst-like structures were demonstrated with TEM in 29 out of 45 (64.4%) patients. Cyst-like structures were constantly associated with other ultrastructural abnormalities commonly observed in chronic inflammation, and were found both in subjects with primary and with secondary ciliary dyskinesia. When considering only patients with bronchiectasis, a significant correlation between prevalence of cyst-like structures and the severity of bronchiectasis was demonstrated. Follow-up (2-22 months) of seven patients demonstrated that in the five children with secondary dyskinesia, the ultrastructural defect completely disappeared and there was a small reduction in the abnormality in the two patients with primary dyskinesia. In contrast to one previous report, the reversibility of the defect suggests its secondary origin, which is most likely related to chronic airway inflammation.

Adolescent↗
PubMed2000

Bartonella henselae and inflammatory bowel disease.

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohn's disease in an adolescent boy. Bartonella henselae infection was diagnosed by specific serology and the patient recovered. Ileitis could be related to B. henselae infection.

Adolescent↗
PubMed2000

Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice.

We investigated the antigenic specificity of the humoral immune response to infection by Salmonella typhimurium, by competitive inhibition enzyme-linked immunosorbent assay and Western immunoblots. A panel of eight murine monoclonal antibodies, raised to OmpC and OmpD porins and lipopolysaccharide (LPS)-O antigens, was used to define the specificity of the polyclonal immune response in mice. The monoclonal antibody panel recognized five distinct epitopes; these were localized to surface-exposed loops of OmpC and OmpD porin, to the "eye-let" forming loop L3 of OmpC/OmpD, and to LPS-O4 and O5 factors. The immune mouse serum raised to infections with S. typhimurium LT-2 strain WB600 (wild-type) competitively inhibited the binding of biotin-labelled monoclonal antibodies to the epitopes that they recognize, indicating that all five epitopes were targets of the host immune response to natural infection. However, only two epitopes, one within a surface-exposed loop of OmpC porin, and the other in the LPS-O4 factor, were immunodominant. Furthermore, the bacterial LPS core and O-antigen structure influenced the immune response to the porins. Surface epitopes of porins were dominant in the rough strain SH5014 (rfa), whereas the immune recognition of LPS epitopes was predominant in mice infected with the smooth, wild-type strain (WB600). Finally, the immune response to LPS epitopes O4 and O5 was more pronounced in mice immunized with heat-killed cells than those infected with live S. typhimurium.

Animals↗
PubMed2000

Widening of the clinical spectrum of Bartonella henselae infection as recognized through serodiagnostics.

UNLABELLED: The recently improved diagnostics have widened, in children, the spectrum of clinical manifestations recognisable as Bartonella henselae infection. We report here the clinical features of 20 (14 males) consecutive children with serologically proved B. henselae infection observed within 12 months in the Paediatric Department of the University of Pisa. The patients had a mean age of 7 years 4 months (range 1.1-14.1 years). All children but one had a history of contact with kittens. Clinical manifestations included regional lymphadenopathy in 14 patients, representing in five the only clinical manifestation at onset, infectious mononucleosis-like syndrome in six, erythema nodosum in three, and Parinaud oculoglandular syndrome in one. In five patients a severe disorder was first suspected: fever of unknown origin in two with multiple hepatosplenic granulomatosis in one; osteolytic lesion suggesting bone neoplasm, marked inguinal lymph-node enlargement, suggesting Burkitt lymphoma, and an acute encephalopathy in one each. Bartonella henselae IgG antibody was positive in all patients with a titre ranging from 1:128 to 1:8590. IgM antibody was present in all except one child with an IgG titre of 1:2048. All patients recovered, some spontaneously. CONCLUSION: Bartonella henselae infection is frequent in Tuscany and probably underdiagnosed due to the high frequency of atypical onset of the clinical manifestations. An accurate clinical history and a reasonably wide use of the serological test may allow a rapid and accurate diagnosis, reassuring the family of the patient and avoiding invasive and expensive diagnostic procedures.

Adolescent↗
PubMed2000

Variable correlation between 6-mercaptopurine metabolites in erythrocytes and hematologic toxicity: implications for drug monitoring in children with acute lymphoblastic leukemia.

Nineteen pediatric patients affected by acute lymphoblastic leukemia (ALL) were examined weekly with respect to 6-mercaptopurine nucleotide (6-MPN) and 6-thioguanine nucleotide (6-TGN) levels in erythrocytes during the course of maintenance treatment with 6-MP 50 mg/m2 per d and results were related to various parameters of bone marrow function to assess, in the same individual, the level of reliability of 6-MP metabolites in predicting a later change in peripheral blood cell counts. Median values for 6-MPN and 6-TGN were 57 and 200 pmol/8 x 10(8) erythrocytes, respectively, as measured by reversed-phase high-performance liquid chromatography (HPLC). 6-TGN levels in erythrocytes were inversely related with white blood cell count (r = -0.463, p < 0.0001, n = 361), absolute neutrophil count (r = -0.386, p < 0.0001, n = 347), erythrocyte (r = -0.354, p < 0.0001, n = 287), and platelet counts (r = -0.24, p < 0.0001, n = 319) in the majority of patients (n = 10-12), while no correlation was found for 6-MPN. In the remaining children, no evidence of correlation was demonstrated between 6-TGN levels and myelotoxicity. The results confirm the role of 6-TGN as the reference cytotoxic metabolite for evaluating the exposure to 6-MP and identifying treatment compliance in ALL children but indicate the limits of a follow-up based solely on metabolite levels and suggest that a more correct approach remains the double monitoring of 6-TGN and blood cell count with differential.

Adolescent↗
PubMed2000

Pseudoinfectious mononucleosis: a presentation of Bartonella henselae infection.

Six children presented during one year with clinical features of infectious mononucleosis, but with laboratory findings of leucocytosis with neutrophilia, increased erythrocyte sedimentation rate, and hypergammaglobulinaemia. Serology for Epstein-Barr virus, cytomegalovirus, adenovirus, and Toxoplasma gondii was negative, while anti-Bartonella henselae IgM with high IgG titre (>/=1/1024) was present in all. All children had contact with kittens. No specific treatment was administered and all recovered.

Bartonella henselae↗
PubMed1999

The c-kit receptor and its ligand stem cell factor in childhood malignant lymphoid precursors.

The c-kit receptor (CD117) and its ligand stem cell factor (SCF) play an important role in the development, differentiation, and survival of normal and malignant hematopoietic cells. The aim of this work is to review the cellular distribution of this receptor and the effect of SCF on the hematopoietic system, particularly among lymphoid lineage, either in normal or malignant cell progenitors. We examined reports and results in the field and articles or abstracts published in journals covered by MEDLINE. Additionally, we evaluated CD117 expression on fresh blast cells of 376 newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL) that were referred to centers affiliated with the Italian Association for Pediatric Hematology and Oncology (AIEOP). In view of our data, approximately 11% of ALL are CD117 positive. In particular, this receptor can be expressed in 10% and 11.5% of T-lineage and B-lineage ALL, respectively. Its expression is associated with an intermediate/mature phenotype in T-lineage ALL, whereas in B-lineage ALL, the majority of the positive cases are classified as early B ALL. The effect of SCF on malignant hematopoiesis and its potential clinical uses are reviewed.

Cell Lineage↗
PubMed1998

Mobilization, collection, and characterization of peripheral blood hemopoietic progenitors after chemotherapy with epirubicin, paclitaxel, and granulocyte-colony stimulating factor administered to patients with metastatic breast carcinoma.

BACKGROUND: As single agents, both paclitaxel and epirubicin in combination with cytokines can mobilize peripheral blood progenitor cells (PBPCs). The authors have demonstrated previously that the combination of epirubicin and paclitaxel is very active against metastatic breast carcinoma and tolerated by patients. METHODS: Twenty-one patients with metastatic breast carcinoma received epirubicin 90 mg/m2 in combination with paclitaxel 200 mg/m2 given as a 3-hour infusion, and granulocyte-colony stimulating factor (G-CSF) starting 24 hours after chemotherapy to mobilize PBPCs. An immunophenotypic analysis for CD3, CD4, CD8, CD 19, CD33, CD34, and CD38 antigen expression was performed on apheresis products. Eighteen patients underwent high dose chemotherapy and were engrafted with PBPCs primed with paclitaxel, epirubicin, and G-CSF. RESULTS: The median number of circulating CD34+ cells at peak was 70/microL; in the patients less heavily pretreated, it was 106.7/microL. The mean number of CD34+, CD34+/CD33-, and CD34+/CD38- cells/kg collected per apheresis was 6.3 x 10(6), 2.0 x 10(6), and 0.18 x 10(6), respectively. The mean number of CD34+ cells/kg per apheresis was 7.8 x 10(6) when the preleukapheresis CD34+ cell count was more than 50/microL and 0.9 x 10(6) when the CD34+ cell count was less than 50/microL. The mean number of CD3+, CD4+, and CD8+ cells/kg collected per apheresis was 90 x 10(6), 50 x 10(6), and 30 x 10(6), respectively. CONCLUSIONS: Epirubicin plus paclitaxel in combination with G-CSF mobilizes PBPCs, including more primitive progenitors capable of supporting myeloablative treatment. Moreover, the mononuclear cells collected in this study contained high levels of cytotoxic effector cells suitable for ex vivo manipulation to augment the antitumor effect.

Adenocarcinoma↗
PubMed1998

Hyperbaric oxygen therapy in a case of post-total body irradiation colitis.

We report a 21-year-old man who experienced symptoms of colitis following autologous TBI-conditioned PBSC transplantation, which persisted despite conventional treatment. Abdominal echography showed a thickened, stratified wall of the cecum, of the right colon and of part of the transverse colon. Hyperbaric oxygen therapy (20 sessions of 100% oxygen inhalation at 2.5 bar for 120 min in a hyperbaric chamber) achieved a prompt clinical recovery as well as complete disappearance of the ultrasound abnormalities.

Abdomen↗
PubMed1996

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine and methotrexate.

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine (6-MP) and methotrexate (MTX) was investigated in patients as well as in rats and in HL-60 human leukemic cells. Ten children affected by acute lymphoblastic leukemia (ALL) in remission received daily doses of 6-MP given at 25 mg/m2 and i.v. infusion of high-dose MTX at 2 or 5 g/m2 once every other week. When 6-MP was given alone, the mean peak plasma concentration (Cmax) and area under the curve (AUC) of 6-MP were 72.5 ng/ml and 225.3 h ng ml(-1). Concurrent treatment with MTX at 2 or 5 g/m2 resulted in a mean increase of 108% and 121% in the Cmax and of 69% and 93% in the AUC, respectively. In rats treated with an oral dose of 6-MP at 75 mg/m2, MTX given i.p. at 5 g/m2 produced mean increases of 110% and 230% in the Cmax and AUC of 6-MP, respectively. In HL-60 human leukemic cells incubated with 6-MP at 250 ng/ml, the cumulative intracellular concentration of 6-thioguanine and 6-MP nucleotides was not significantly modified by treatment with 20 micrograms/ml of MTX. The present findings indicate that high-dose MTX enhances the bioavailability of 6-MP as evidenced by the observed increases in the plasma Cmax and AUC of 6-MP in humans and animals.

Adolescent↗
PubMed1994

[Brief analytical review of additional possible mechanisms in the pathogenesis of AIDS].

It is generally agreed that HIV itself has the primary role in the initiation and propagation of the pathogenic process of the infection. Nonetheless, a number of important issues concerning the pathogenesis of HIV infection remain unresolved. For example, it remains unclear how CD4+ T cells are lost after HIV infection. The low frequency of infected cells seen even in advanced infection implies that a direct cythopathic effect of HIV on infected CD4+ T cells cannot explain their disappearance. Multiple and diverse mechanisms have been proposed as supplements to the HIV in the destruction of CD4+ cells and the pathogenesis of AIDS. However, it is not yet possible to state confidently which additional mechanism(s) is important. Identification of the nature of this supplemental process has become essential for successful, non-harmful intervention. We propose here a short analytical review of the possible supplemental mechanisms of immunological destruction in AIDS in order to emphasize the complexity of the pathogenesis of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P < 0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

Adolescent↗
PubMed1988

Etoposide in recurrent childhood Langerhans' cell histiocytosis: an Italian cooperative study.

Eighteen evaluable children with recurrent Langerhans' cell histiocytosis (LCH) which was resistant to standard therapy, were treated with etoposide (VP 16-213), 200 mg/m2/day for 3 days every 3 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses were demonstrated in 15 patients (83.3%). Only one of the 12 children achieving a complete remission has relapsed. No dose-limiting major toxicities were registered. Although etoposide might be an effective treatment in recurrent LCH which needs a chemotherapeutic approach, it is emphasized that this drug must be used carefully.

Child↗