Low dose cytosine arabinoside in the treatment of acute non-lymphocytic leukemias and myelodysplastic syndromes.
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Biomedical subjects
Publications and source records attributed to S Mansueto.
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The ability of PBMC from eight patients with confirmed visceral leishmaniasis (Leishmania donovani) to produce IL-2 in response to PHA in vitro was investigated. PBMC from the patients produced significantly lower levels of IL-2 and had reduced proliferative response to PHA at the time of disease diagnosis compared with healthy controls. Their ability to produce IL-1 in response to LPS was, however, unaltered. The patients also showed normal levels of OKT4+ and IL-2R+ cells in the peripheral blood, as judged by specific immunofluorescence staining. All patients were given antimony therapy, and five were cured. The recovered patients showed significant improvement in the IL-2 producing capacity of their PBMC. The PBMC preparations of patients and controls were cryopreserved before and after successful chemotherapy on the patients. The frozen cell preparations were thawed and viable autologous cells cocultured with equal numbers of PBMC from patients before and after chemotherapy. The frozen cells from five healthy controls showed little or no difference whether they were cultured together or separately. In contrast, coculturing of cells from the five recovered patients with autologous pretreatment cells produced significantly and consistently lower levels of IL-2 compared with those produced when the cells were cultured separately. These results therefore demonstrate that the PBMC from patients with visceral leishmaniasis contain a population of cells that are capable of suppressing the IL-2 production by autologous PBMC from recovered patients. The method of cryopreservation should be useful for studying the immune regulation in this and other clinical diseases in vitro.
Prospective investigation of cutaneous lesions of 24 Sicilian patients revealed that 17 were taches noires from patients with a documented diagnosis of boutonneuse fever. Immunofluorescent Rickettsia conorii were demonstrated in 14 of 17 taches noires. The major pathologic lesions observed were a moderate-to-severe lymphohistiocytic vasculitis (17 of 17 cases), generally moderate dermal edema (17 of 17 cases), and cutaneous necrosis (12 of 16 cases). In contrast with previous observations of eschars in Rocky Mountain spotted fever, thrombosis was usually absent (nine of 17 cases) or inconsequential (five of 17 cases). Thus, it appears that the pathogenic mechanism of the ischemic necrosis is not thrombosis, suggesting either compression of the microcirculation by the dermal edema or another mechanism. Review of the biomedical literature related to eschars and cutaneous arthropod bites strongly argues against a pathogenetic contribution of the tick bite itself other than the intradermal inoculation of rickettsiae. The tache noire offers an excellent, accessible model for the study of the human-rickettsia interaction, including the pathogenic mechanisms leading to necrosis and the immune mechanisms resulting in killing the rickettsiae.
Pairs of cases of Boutonneuse Fever (BF) occurred in three families. The illness appeared almost simultaneously in both members of each family, but was generally more serious in one as judged by clinical and laboratory parameters. The possibility of a "bed rickettsiosis", that is reactivation of rickettsiae by the blood meal obtained from the first individual by the same tick which fed upon the second individual, could be excluded in two of the three pairs of cases. In only one of the case pairs were the individuals sharing the same bed. The differences in severity of symptoms may be related to the different immunological pattern observed in these patients. Previous rickettsial infection may have provided partial immune protection, as is repeatedly reported in the literature. In one couple, the more seriously ill patient had antibodies of the IgM class, suggesting that this was his first exposure to Rickettsia conorii. The less severely ill patient had antibodies of the IgG class only, presumably as the result of re-exposure after previous asymptomatic infection with spotted-fever-group rickettsia.
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The history of Q fever in Italy may be divided into three periods: epidemic in character after the Second World War, endemic occurrence from 1960 to 1980, and sporadic occurrence at present. Clinical symptoms are unspecific, and diagnosis must be confirmed by serology and isolation of the causative agent. The reported incidence is consequently underestimated. Results are reported of a seroepidemiologic survey in animals and humans in the Italian region and western Sicily. In the Mediterranean area several epidemic foci are still present. The need of further studies to evaluate the incidence of Q fever and to shed more light upon the epidemiology of Coxiella burnetii infections is stressed.
The isolation of a Spotted Fever Group (SFG) Rickettsia "Mortilli strain" from brown dog ticks Rhipicephalus sanguineus removed from dogs associated with a confirmed case of Boutonneuse Fever (BF) in a site of a Western Sicily is reported. The need is stressed for isolation and adaption on cell cultures of SFG rickettsial strains for analysis of antigenic structure employing modern methodology.
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The distribution and prevalence of spotted fever group rickettsial infection in the ixodid dog tick Rhipicephalus sanguineus were found to occur at a rate of 19.7% with variation related to geographic and sociooccupational factors. A higher rate of infection was demonstrated in ticks removed from dogs associated with documented cases of boutonneuse fever. The results fit into available clinical and seroepidemiologic data on Rickettsia conorii infection in western Sicily.
A clinical epidemiological survey of Legionella pneumophila infections occurring in Italy between 1 December 1985 and 31 May 1986 was carried out to evaluate the incidence of sporadic, epidemic and nosocomial L. pneumophila pneumonia. A total of 355 cases of pneumonia were studied of which 11.5% were due to Gram positive bacteria, 11% were due to Gram negative bacteria, 7.9% were due to Mycoplasma pneumoniae, 4.5% were due to L. pneumophila and 8.5% were due to sundry aetiological agents. The remainder (45.6%) could not be diagnosed accurately. In addition, the anti L. pneumophila antibody titres were assessed. The results are discussed in terms of the occurrence of the disease in Italy and regarding the importance of considering the possibility of legionellosic aetiology when diagnosing pneumonia.
Seven consecutive Sicilian patients with boutonneuse fever but without clinical symptoms of hepatic disease underwent hepatic biopsy and had similar hepatic lesions. Foci of hepatocellular necrosis were infiltrated with predominantly mononuclear leukocytes. No intact Rickettsia conorii were identified in the tissues by immunofluorescence. The apparent high frequency of viscerotropism in boutonneuse fever conforms to the recent observations of severe illness in what had often been described previously as a benign rickettsiosis.
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Spotted fever group Rickettsiae were isolated from dog ticks (R. sanguineus) removed from dogs in different areas of western Sicily.
Circulating immune complexes (CIC) occurred in 36% of a group of 25 patients with Fièvre boutonneuse. CIC were present only in the first week of the disease and there was no evidence of other humoral immunological abnormalities or alterations of the coagulation factors studied. The presence of CIC was not associated with a more severe clinical manifestation or with symptoms or tissue injuries. It is considered that CIC do not play a major role in Fièvre boutonneuse.