Francesco Saverio Vella

Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging

Neutrophil respiratory burst was assessed on plates coated with fibronectin (FN) or laminin (LM), both used at dosages inhibiting polystyrene-triggered cell activation in young healthy volunteers. Under these conditions, a low, yet significant, spontaneous superoxide anion (O(2)(-)) production, matching with enhanced levels of basal adherence, was detected in FN-plated neutrophils of elderly donors. In contrast, although neutrophil stimulation with tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), fMLP or phorbol myristate acetate (PMA) gave rise to a massive and prolonged FN-primed O(2)(-) release, a significant impairment of oxidative response occurred in the aged group as a result of GM-CSF or fMLP cell challenge. Such an effect was not associated to an age-related imbalance of stimulant-triggered neutrophil adhesiveness to FN, even though a larger contribution of CD18-dependent versus CD18-independent pathways was observed in old as compared to young individuals. Notably, within the aged group, anti-CD18 monoclonal antibody cell pretreatment resulted in a higher suppression of FN-primed O(2)(-) release following TNF-alpha with respect to GM-CSF stimulation, thus implying that an agonist-related defect of the coupling between beta2 integrin-dependent adhesive and oxidative events is likely to occur as a feature of age. All physiological mediators failed to activate the respiratory burst of neutrophils plated on LM-coated wells in both young and aged donors. This effect appears to be the result of an active process, since neutrophils from either group of subjects adhered to LM-coated surfaces and LM inhibited in a dose-dependent manner the FN-priming effect on neutrophil O(2)(-) production. All together the findings provide additional evidence for an imbalance of neutrophil-mediated functions in the elderly.

Prevalence of antibodies to hepatitis C virus among family members of patients with chronic hepatitis C

In this study, 108 family members of 40 chronically HCV-infected patients (19 post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies were found in 16 (14.8%) families of anti-HCV positive index cases (15% males and 14.6% females; p = NS), with no difference between families of index cases with post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV positive family members, 12 (75%) had clinical and/or serological evidence of chronic liver damage. None of the control group subjects were anti-HCV-positive (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies were not detected among parents. We found a positive correlation between the prevalence of anti-HCV antibodies among families and the severity of the HCV-related chronic liver damage of the index cases (p < 0.00005). In addition, to confirm that HCV infection and HCV-related chronic hepatitis may be transmitted intrafamiliarly, our findings also indicate that horizontal, especially sexual contact, is a more important route of HCV infection than vertical/perinatal transmission. Finally, the risk of acquiring HCV infection among families appears to be the highest when index cases are suffering from severe HCV-related chronic hepatitis.

Drug reaction with eosinophilia and systemic symptoms caused by lenalidomide.

ejd.2012.1853 Auteur(s) : Caterina Foti1 c.foti@dermatologia.uniba.it, Annarita Antelmi1, Antonio Mazzocca2, Francesco Saverio Vella2, Paolo Romita1, Stefania Pugliese3, Daniela Lomazzo3, Piero Portincasa3, Giuseppe Palasciano3 1 Section of Dermatology, Department of Biomedical Sciences and Human Oncology, 2 Department of Emergency and Organ Transplantation, 3 Clinica Medica Augusto Murri, Department of Biomedical Sciences and Human Oncology University of Bari Medical School, 70124 Bari, Italy Drug [...]

Palmodigital purpura as the only skin abnormality in myeloma-associated systemic amyloidosis.

A diagnosis of Bence–Jones multiple myeloma (k type) in a 69-year-old housewife was initially made in 1992. She responded well to melphalan and prednisone chemotherapy. In 2002, she presented with an 8-month history of bone pain, concurrent severe paresthesia on the radial side of the hands especially at night, and cutaneous non-palpable purpura of the palmodigital regions predominantly localized on the fingers (top), without thrombocytopenia or clotting disturbances. Minimal trauma, such as turning pages or rubbing her hands, appeared to precipitate formation of the purpuric lesions. Laboratory findings included: haemoglobin 10 g ⁄ dl, Bence–Jones proteinuria 3 g ⁄24 h, albuminuria 2AE6 g ⁄24 h, b2 microglobulin 30 mg ⁄ l and 37AE5% bone marrow plasma cells infiltration, leading to a diagnosis of relapsed myeloma. Capillaroscopy showed a microangioitic pattern of the fingernail capillary bed. Moreover, the subpapillary plexus was visible, due to atrophy of the dermis (bottom). An ultra-sound scan and electromyography identified carpal tunnel syndrome. A biopsy specimen of clinically normal-looking skin showed Congo red-positive eosinophilic material in the reticular dermis and within the blood vessel walls. Immunohistochemical stains were positive for k light chains. A diagnosis of amyloid-related purpura was made. Other disorders that share similar clinical features and localization in friction areas (steroid-induced purpura, senile purpura or paraproteinaemic purpura) were excluded by histological and immunohistochemical methods. In conclusion, we describe a case of myeloma-associated systemic amyloidosis, which presented with unusual cutaneous lesions, i.e. palmodigital purpura of the hands. Skin involvement is a relatively rare manifestation in myeloma-associated amyloidosis, but it may precede more typical signs of amyloidosis and a simple skin biopsy can aid diagnosis.