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Biomedical subjects

M Boni

Publications and source records attributed to M Boni.

At least 19 recordsLinked to original sources

A combined bovine herpesvirus 1 gB-gD DNA vaccine induces immune response in mice.

Although DNA vaccines have several advantages over conventional vaccines, antibody production and protection are often not adequate, particularly in single plasmid vaccine formulations. Here we assessed the potential for a combined vaccine based on plasmids encoding the membrane-anchored or secreted forms of bovine herpesvirus type 1 (BHV-1) glycoprotein B and D (gB and gD) to induce neutralizing and cell mediated immune responses in mice. Animals were injected by intramuscular, subcutaneous and intranasal routes. Mice immunized with the combined vaccine containing the secreted forms of BHV-1 glycoproteins developed higher titers of anti-BHV-1 neutralizing antibodies, compared to wild type gB/gD combined plasmids and to single plasmid injected groups. Cellular immunity was also developed in mice immunized with combined vaccines, whereas low or no response were observed in single plasmid injected animals. The data suggest the potential use of this combined vaccine in in vivo trials of calves, in order to evaluate its protective efficacy.

Administration, Intranasal↗

Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution.

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q- showed a better survival than the poor IPSS cytogenetic category (P=0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del(7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage.

Aged↗

Assay of fipronil efficacy to prevent canine monocytic ehrlichiosis in endemic areas.

Our objective was to evaluate the efficacy of fipronil for the prevention of Ehrlichia canis transmission to dogs by Rhipicephalus sanguineus in two endemic areas situated in Africa (Dakar and Djibouti). We carried out controlled trials in kennels for 1 year on 248 dogs, mainly police dogs and military working dogs. Eight groups were studied in a multi-centre study. Fifty five fipronil treated dogs were located in two separated kennels (G3, 37 dogs in Djibouti and G8, 18 dogs in Dakar). G1 (66 dogs) and G2 (60 dogs) were untreated control groups located in Djibouti, whereas G4 (32 dogs), G5 (13 dogs), G6 (18 dogs) and G7 (4 dogs) were the control groups located in Dakar. The epidemiological status of each group is known. G1 and G2 dogs were not kept in kennels, whereas G3, G4, G5, G6, G7, G8 dogs were housed in equivalent kennels. Tick infestation, clinical status and Ehrlichia seroprevalence were assessed during 1 year (duration of the study). Dog treated with fipronil showed neither canine monocytic ehrlichiosis (CME) nor tick infestations. In all groups of untreated control animals, R. sanguineus tick infestations were frequent, particularly in kennels (G5, G6 and G7) as well as morbidity and mortality due to CME. E. canis infection rates were low for fipronil treated animals: 2.7% (1/37) for G3 and 5.5% (1/18) for G8 group. Among control animals, seroprevalence was maximum (100%) in dogs kept in kennels (G5, G6 and G7 groups) and high among native dogs in Djibouti (G1 group): 69.7% (46/66) and in Dakar (G4 group): 50% (16/32). Dogs belonging to expatriate citizens (G2 group) were less likely to be infected: 21.7% (13/60). The comparison of serological results among French army dogs and French citizen dogs that were introduced in Djibouti for an average of 10 months shows a statistically significant (P<0.001) difference. Among fipronil treated animals (G3 group), 2 dogs out of 55 seroconverted (3.6%) compared to 13 out of 60 dogs (21.7%) in the control G2 group. The results of our study indicate the preventative efficacy of a fipronil monthly treatment to avoid CME in endemic areas. Epidemiological data concerning animals that live in the same endemic areas are an example of the serious consequences (in terms of mortality and morbidity) that are related to the absence of efficient methods for tick-control. In order to protect dogs that are in transit in endemic areas against tick-transmitted diseases, the use of an adapted acaricide product is recommended.

Africa↗

Is FISH a relevant prognostic tool in myelodysplastic syndromes with a normal chromosome pattern on conventional cytogenetics? A study on 57 patients.

Conventional cytogenetics (CC) at clinical diagnosis shows a normal karyotype in 40-60% of de novo myelodysplastic syndromes (MDSs). Fluorescence in situ hybridization (FISH) might detect occult aberrations in these patients. Therefore, we have used FISH to check 57 MDS patients who were karyo-typically normal on CC. At clinical diagnosis, FISH revealed a clonal abnormality in 18-28% interphase cells from nine patients, five of whom also presented the same defect on metaphase FISH. In five out of nine patients, the occult defect effected a change in the international prognostic scoring system (IPSS). An abnormal FISH pattern was significantly correlated with marrow blast cell percentage (P<10(-3)) and IPSS (P<10(-3)). Patients with an occult abnormality showed an overall survival and event-free survival significantly inferior in comparison to those of patients with normal FISH (P<10(-3), P<10(-3)). Death and AML progression were 15- and eight-fold more frequent in FISH abnormal patients. In conclusion, occult defects (1) are revealed in about 15% of CC normal MDS patients, (2) are overlooked by CC either because of the poor quality of metaphases or their submicroscopic nature, (3) are clinically relevant as they may cause a change in the IPSS category and may identify a fraction of CC normal patients with an unfavorable clinical outcome.

Adult↗

Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea.

ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hydroxyurea (HU). Pipobroman (PI), a well tolerated and simple to use drug, constitutes a valid alternative to those cytoreductive treatments. The present study reports on 155 ET patients treated at our institution from 1985 to 1995, and monitored until December 2000. A good control of thrombocytosis was achieved with PI as the only treatment in 106 patients and with HU in 23 patients. Twenty-six patients received no treatment. After a median follow-up of 104 months, seven patients (four treated with HU, and three with PI) developed AML whereas one patient treated with PI developed MDS. A significant difference in progression-free survival was observed between HU- and PI-treated patients (P = 0.004). A short-arm deletion of chromosome 17 was most frequently detected in HU-treated patients, while a long-arm trisomy of chromosome 1 and a monosomy 7q were seen in PI-treated patients. No TP53 mutation was discovered in the six patients studied (two HU-treated and four PI-treated). We conclude that these cytogenetic abnormalities are not linked to the natural history of the disease, but rather that they might be induced by the cytoreductive treatment.

Acute Disease↗

Lack of correlation between Bartonella DNA detection within fleas, serological results, and results of blood culture in a Bartonella-infected stray cat population.

OBJECTIVE: To correlate the presence of different Bartonella species in the blood of a stray cat population trapped on a French military base with specific antibodies and species detected in cat fleas. METHODS: The prevalence of Bartonella bacteremia was investigated in 61 cats by plating frozen whole blood on blood agar plates. Identification of isolates and detection of Bartonella DNA from cat flea batches from ten cats was achieved by PCR amplification and sequencing. Antibody detection was performed by microimmunofluorescence. RESULTS: We obtained 38 isolates of Bartonella from blood. Sixteen were identified as B. clarridgeiae, 15 as B. henselae genotype/serotype Houston 1 (type I), and seven as B. henselae genotype/serotype Marseille (type II). B. henselae was detected in five fleas, and B. clarridgeiae in one flea. Sixty-one per cent of the cats had detectable antibodies against at least one species or serotype. Sixteen cats had antibodies against only one antigen. For each species, the distribution of bacteremia among the cats could not be correlated with either the distribution of infected fleas or the distribution of specific antibodies. CONCLUSIONS: The lack of correlation between Bartonella DNA detection within fleas, serological results, and results of blood culture is probably due to a lack of natural heterologous protection between species or serotypes. Cats suffer bacteremia with three Bartonella species and should therefore be considered the reservoirs of at least three human pathogens.

Animals↗

The sandfly fauna in the visceral-leishmaniasis focus of Gedaref, in the Atbara-River area of eastern Sudan.

Visceral leishmaniasis (VL) is an acute public-health problem in Sudan. Between 1997 and 2000, four, brief entomological surveys were carried out in Barbar El Fugarra, a village in the state of Gedaref, in the Atbara-River area of eastern Sudan. Between 1996 and 1999, 658 cases of VL occurred among the village's population of about 4000. CDC miniature light-traps set inside and outside human dwellings were used to collect a total of 12,745 sandflies, including five species of the genus Phlebotomus and 19 of Sergentomyia. Phlebotomus papatasi and P. orientalis made up 7% and 5% of the collected sandflies, respectively. Seasonal variation was observed in the numbers of P. orientalis, P. papatasi, S. schwetzi and S. magna caught. Almost all (88%) of the sandflies collected were caught inside houses or granaries and there appeared to be particularly large indoor populations of P. orientalis, P. papatasi, S. schwetzi, S. magna and S. clydei. Phlebotomus orientalis could be responsible for the indoor transmission of the parasites causing the local VL, between humans and between humans and local dogs (which have been found infected by some of the Leishmania zymodemes found in humans). The co-occurrence in this focus of P. papatasi and Arvicanthis niloticus, which are known vectors and reservoir hosts, respectively, of L. major, indicates the possibility that outbreaks of human cutaneous leishmaniasis might occur in the area.

Animals↗

Human herpesvirus 7 is latent in gastric mucosa.

Chronic gastritis is associated frequently with persistent infection by Helicobacter pylori. However, not all patients with chronic gastritis have evidence of H. pylori infection, suggesting that other factors might contribute to the development of gastritis. The present study was undertaken to evaluate a possible etiologic role of human herpesvirus 7 (HHV-7). HHV-7 DNA was detected in about 80% of gastric biopsies, both in healthy mucosa from individuals without evidence of inflammation and in biopsies from patients with histologically confirmed chronic gastric inflammation. HHV-7 was present also in H. pylori negative samples, was associated specifically with gastric tissue and not with residual blood within the mucosa, and was present with high viral loads. HHV-7 DNA persisted in several patients also after remission of gastric inflammation and the viral presence did not correlate with specific symptoms. Analysis by RT-PCR showed that HHV-7 is transcriptionally inactive in chronic gastritis lesions. These observations show that gastric tissue represents a site of HHV-7 latent infection and a potential reservoir for viral reactivation.

Biopsy↗

The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia--analysis of 848 patients.

We studied the impact of cytogenetics and kind of induction/consolidation therapy on 848 adult acute myeloid leukemia (AML) patients (age 15-83). The patients received three types of induction/consolidation regimen: standard (daunorubicin and cytosine arabinoside (3/7); two cycles); intensive (idarubicin, cytosine arabinoside and etoposide (ICE), plus mitoxantrone and intermediate-dose Ara-C (NOVIA)); and low-dose (low-dose cytosine arabinoside). CR patients under 60 years of age, if an HLA-identical donor was available received allogeneic stem cell transplantation (allo-SCT); otherwise, as part of the program, they underwent autologous (auto)-SCT. CR rates significantly associated with 'favorable' (inv(16), t(8;21)), 'intermediate' ('no abnormality', abn(11q23), +8, del(7q)) and 'unfavorable' (del (5q), -7, abn(3)(q21q26), t(6;9), 'complex' (more than three unrelated cytogenetic abnormalities)) karyotypes (88% vs 65% vs 36%, respectively; P = 0.0001). These trends were confirmed in all age groups. On therapeutic grounds, intensive induction did not determine significant increases of CR rates in any of the considered groups, with respect to standard induction. Low-dose induction was associated with significantly lower CR rates. Considering disease-free survival (DFS), multivariate analysis of the factors examined (including karyotype grouping) showed that only age > 60 years significantly affected outcome. However, in cases where intensive induction was adopted, 'favorable' karyotype was significantly related to longer DFS (P = 0.04). This was mainly due to the favorable outcome of t(8;21) patients treated with intensive induction. Patients receiving allo-SCT had significantly longer DFS (P = 0.005); in particular, allo-SCT significantly improved DFS in the 'favorable' and 'intermediate' groups (P = 0.04 and P = 0.048, respectively). In conclusion our study could provide some guidelines for AML therapy: (1) patients in the 'favorable' karyotype group seem to have a longer DFS when treated with an intensive induction/consolidation regimen, adopted before auto-SCT instead of standard induction; this underlines the importance of reinforcement of chemotherapy, not necessarily based on repeated high-dose AraC cycles. Allo-SCT, independently of induction/consolidation therapy, should be considered an alternative treatment; (2) patients in the 'intermediate' karyotype group should receive allo-SCT; (3) patients in the 'unfavorable' karyotype group should be treated using investigational chemotherapy, considering that even allo-SCT cannot provide a significantly longer DFS, but only a trend to a better prognosis.

Adolescent↗

Trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.

We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with +11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.

Aged↗

Translocation (8;16) in a patient with acute myelomonocytic leukemia, occurring after treatment with fludarabine for a low-grade non-Hodgkin's lymphoma.

We describe a 65-year old woman who developed a t(8;16)(p11;p13) positive acute myeloid leukemia (AML)-M4 without a prior myelodysplasia thirty-six months after a low-grade non-Hodgkin's lymphoma treated with alkylating agents (chlorambucil and cyclophosphamide) and fludarabine, a purine analog with a significant activity in lymphoproliferative disorders. The t(8;16)(p11;p13) is present in 0.4% of AML of M4-M5 cytotype. In the present case it was identified by conventional cytogenetics; involvement of the MOZ and CBP genes was demonstrated by fluorescence in situ hybridization, but not by reverse transcription polymerase chain reaction. The patient died of sepsis after the first course of induction chemotherapy. This is the first t(8;16) AML-M4 arising after fludarabine treatment of which the leukemogenic role in our case is very difficult to ascertain. Most t(8;16) t-AML cases had received anthracyclines with or without cyclophosphamide; none was ever administered chlorambucil. Our patient was never given anthracyclines and the cumulative doses of chlorambucil and cyclophosphamide employed were low.

Aged↗

[Triage in first-aid: is it necessary or indispensable?].

The priorities of a modern emergency care unit with more than 20,000 patients/year are analysed underlining that only a professional organization can offset the increasing demand of the population. The importance of a pre-evaluation of the patients in a triage unit to privilege the real emergency cases is underlined. These emergency units also need an information network in a real-time contact with the nearby sanitary structures and the Operative Center. This for a faster hospitalization of the patients who need it. The opportunity to improve the contacts between the family doctor and the Hospital to a better use of the Sanitary System is stressed.

First Aid↗

A complex translocation (5;7) in a patient with acute nonlymphocytic leukemia evolved from a myelodysplastic syndrome.

Complete or partial monosomy for the long arms of chromosomes 5 or 7 or both is frequently observed in therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia. Sporadic cases have been reported in which partial monosomy is due to unbalanced translocations. The patient described herein carries one such rearrangement. 46,XY,t(1;2) (q32;p23),del(5)(q13),der(7)(5qter-->5q22::7p15-->7 q21:),del(12)(p12), resulting in partial monosomy for the long arms of chromosomes 5 and 7 and in partial monosomy for the short arm of chromosome 7.

Chromosome Deletion↗

Survey of seroprevalence of Q fever in dogs in the southeast of France, French Guyana, Martinique, Senegal and the Ivory Coast.

A serological survey was carried out on 429 dogs belonging to the French military in France, French Guyana, Martinique, Senegal and the Ivory Coast. Serology against phase I and II antigens of Coxiella burnetii, the intracellular zoonotic bacterium was performed using indirect immunofluorescence techniques. Specific antibodies were found in dogs from France (9.8%), Senegal (11.6%), Ivory Coast (8.3%), French Guyana (5.2%) but not in those from Martinique. The seroprevalence among 77 dogs who had contact with sheep compared with 352 dogs who had had no contact, demonstrated a significantly higher seroprevalence in the former. Our results indicate that dogs, living close to sheep, may be infected by Coxiella burnetii and should be considered as possible sources of infection for humans.

Animals↗

The invasive behaviour of Cryptococcus neoformans: a possibility of direct access to the central nervous system?

Cryptococcocal meningoencephalitis is always considered secondary to initial lung infection. Because of the unquestionable evidence of haematogenious spread from the lungs, few publications have reported about other possible primary sites of infection or other routes to the central nervous system. This study was designed to investigate the infiltrative pattern of C. neoformans in immunocompromised mice by treatment with dexamethasone. The infection was performed by nasal instillation (30 mice) or injection into the retro-orbital space (12 mice). From the group infected intranasally, 3 mice presented diffuse invasive fungal colonisation of the mucosa and submucosa. The histologic findings showed infiltrative growth along the periosteum, sometimes surrounded nervous endings of submucosa, invasion along the olfactory nerve and simultaneous meningeal involvement in 2 mice on the 6th and 8th day of infection. All mice infected into the retro-ocular space developed lesions containing numerous cryptococci in the local of the inoculum. Out of the main lesion we observed preferential growth along the perineural spaces with adherence to the perineurium, perivascular spaces and sometimes along aponeurosis. Simultaneous invasion of trigeminal ganglio and trigeminal branches was observed in 4 mice. These morphologic patterns suggest the hypothesis of direct infiltrative invasion of the central nervous system.

Administration, Intranasal↗