Francesco Massei

Systemic Bartonella henselae infection with hepatosplenic involvement.

BACKGROUND Systemic manifestations of Bartonella henselae infection are rare in the immunocompetent host. The infection generally has initial symptoms of prolonged fever and multiple granulomatous lesions in liver and spleen. METHODS Retrospective analysis of the records of all patients with hypoechogenic lesions in the liver and/or spleen diagnosed from 1990 through 1996 in three pediatric clinics in northern Italy. RESULTS Among the 13 patients reviewed, 9 had evidence of B. henselae infection and hepatosplenic involvement: five had prolonged and unexplained fever lasting from 3 to 16 weeks, and four had typical cat-scratch disease and peripheral lymphadenitis. All patients had increased sedimentation rate and normal aminotransferase serum activity. Five children had a liver biopsy, by laparotomy in three and by needle in two. In all, the predominant liver lesion was a necrotizing granuloma. All patients were treated with broad-spectrum antibiotics. Fever lasted from 3 to 16 weeks, and hepatic and splenic lesions resolved in all with residual splenic calcification in one. CONCLUSIONS Systemic B. henselae infection represents an important cause of inflammatory hypoechogenic hepatosplenic lesions in children. Serology provides rapid diagnosis, avoiding multiple and invasive investigations. Hepatosplenic involvement can be found even in children with typical cat-scratch disease without apparent systemic manifestations. The frequency of liver and/or splenic involvement in cat-scratch disease is probably underestimated.

Enumeration of human peripheral blood dendritic cells throughout the life

Human aging is associated with immunosenescence, a process characterized by alterations in numerical and functional features of immune system components. Dendritic cells (DCs) are the main antigen-presenting cells, playing a pivotal role in adaptive and innate immunity. Therefore, we investigated the distribution of human circulating DCs throughout the life, in order to contribute to the knowledge of the physiological background underlying the aging of immune system. Cytofluorimetric analysis of peripheral blood samples by all-aged healthy population showed a significant decrease of circulating DCs and of their two main subsets among age. This reduction was limited to the plasmacytoid cell subtype when young and old subjects were analyzed separately. The analysis of circulating Treg cell number in a cohort of the subjects showed a significant reduction with increasing age and a positive significant correlation to myeloid or plasmacytoid absolute numbers. In conclusion, this work provides a large set of data of normal reference values of peripheral blood dendritic cells in healthy population suitable for comparative clinical studies concerning pathological immune dysfunctions.

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

Abstract 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; osteolityc 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. ConclusionBartonella 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.

High Prevalence of Antibodies to Bartonella henselae among Italian Children without Evidence of Cat Scratch Disease

Few data are available on the seroprevalence of antibodies to Bartonella henselae among children. We retrospectively evaluated the presence of immunoglobulin G and M class antibodies to B. henselae in 508 children living in central Italy who were apparently free of any features suggesting B. henselae infection. We found that B. henselae infection is common among children in central Italy, occurs early in life, is in most cases asymptomatic, and resolves spontaneously.

Everolimus Is a Potent Inducer of Erythroid Differentiation and γ-Globin Gene Expression in Human Erythroid Cells

We studied the effects of everolimus on the erythroid differentiation of human leukaemic K562 cells and on the cultures of erythroid progenitors derived from the peripheral blood of β-thalassaemia patients. A quantitative real-time reverse-transcription polymerase chain reaction assay was employed for the quantification of the accumulation of globin mRNAs. The results obtained demonstrate that everolimus is a potent inducer of the erythroid differentiation of K562 cells. Erythroid induction is associated with an increase in α- and γ-globin mRNAs. In erythroid precursor cells from 4 β-thalassaemia patients, everolimus stimulated a preferential increase (ranging from 1.8- to 7.2-fold) in γ-globin mRNA. Only minor effects were observed on the expression of α-globin genes. These results, in our opinion, are of interest as this compound is already employed in clinical trials as an anti-rejection agent following kidney transplantation. These data suggest that everolimus warrants further evaluation as a potential therapeutic drug in the treatment of β-thalassaemia.

Immunological Evaluation of Patients with Beta-Thalassemia major

Abnormalities in the immune system and zinc homeostasis in patients with β-thalassemia major (TM) have been reported. Since zinc ion is essential for the efficiency of the immune system and is required to induce biological activity to thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22 normal controls of the same age. Inhibitory molecules anti-thymulin and the distribution of lymphocyte subsets were also analyzed. Patients with TM presented significantly lowered plasma zinc and thymulin levels when compared to normal subjects. The significant enhancement of the active form of the hormone after zinc addition in vitro suggests that low thymulin values found in TM are due not to a thymic failure in synthesizing and secreting the thymic hormone, but a defect in zinc saturation of the hormone. An impairment of cell subset distribution was also demonstrated. This study shows that zinc and thymulin deficiency contribute to the complex mechanisms underlying immune dysfunction in TM.

Bartonella henselae and inflammatory bowel disease.

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohns 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.

Cholestasis as a presenting feature of acute Epstein- Barr virus infection

Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is common but clinical features of cholestasis are rare in children. We present three children with cholestasis as a presenting feature of Epstein-Barr virus disease.

A Novel Frameshift Mutation (+A) at Codon 18 of the β-Globin Gene Associated with High Persistence of Fetal Hemoglobin Phenotype and δβ-Thalassemia

We report in this paper a novel thalassemia mutation (insertion of a single A nucleotide within the exon 1, at codon 18, of the β-globin gene) associated with a deletion of the δβ-globin gene region, in a patient exhibiting high persistence of fetal hemoglobin. The novel mutation causes a frameshift with the generation of a UGA stop codon. Analysis of the parent’s DNA demonstrates that the A insertion and frameshift mutation are inherited from the father, while the δβ-globin gene deletion is inherited from the mother. Gene dosage analysis and deletion-specific PCR demonstrate that the deletion is the (δβ)⁰ Sicilian deletion, involving a 13.4-kb δβ-globin gene region.

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.