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Biomedical subjects

M Lessard

Publications and source records attributed to M Lessard.

82 records · Page 5Linked to original sources
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In utero fetal liver cell transplantation without toxic irradiation alleviates lysosomal storage in mice with mucopolysaccharidosis type VII.

Lysosomal storage diseases, such as Mucopolysaccharidosis type VII (MPS VII), cause progressive loss of mobility and intellect and result in early death. Treatment of progressive diseases must occur before the blood-brain barrier closes. In MPS VII mice, normal donor hematopoietic cells secrete the missing enzyme beta-glucuronidase (GUSB) that reverses disease manifestations. Correction of lysosomal storage is limited to the visceral organs unless transplantation is preceded by high-dose irradiation. We hypothesize that irradiation opens the blood-brain barrier allowing passage of corrective cells. Here we transplanted genetically myeloablated MPS VII fetuses to determine whether earlier treatment without toxic irradiation is systemically corrective. Cells with a selective advantage in utero were identified. Donor fetal liver cells (FLC), a substitute for difficult to obtain murine cord blood cells, were increased 10-fold in the host peripheral blood over equivalent numbers of adult marrow cells injected simultaneously and were stable long term in both primary and secondary hosts. GUSB- MPS VII fetuses injected with GUSB+ FLC were assessed longitudinally after birth. Donor FLC replaced host stem cell descendants, prolonged life dramatically, and reduced bone dysplasia and lysosomal storage in all tissues long term. GUSB, donor leptomeningeal cells, and microglia were present in the brain at 11 months postinjection. Lysosomal storage in cortical neurons and glia, although not completely corrected, was reduced. We conclude that in utero intervention without toxic pretreatment in this model reduces the storage disease long term and improves the length and quality of life despite exerting only minor effects on the brain.

Animals↗
PubMedDate not supplied

Computerized measurement of Doppler flow velocity waveforms: validation of a new system.

Manual measurement of Doppler flow velocity waveforms is time-consuming and carries unavoidable and significant intraobserver and interobserver variability. Those drawbacks limit the routine use of Doppler-derived indexes of systolic and diastolic function. This report describes a system that performs automatically all relevant measurements currently obtained from mitral, tricuspid, aortic, and pulmonary waveforms. One hundred and sixty waveforms, obtained from patients whose ages ranged from a 19-week fetus to a 21-year-old adult, were measured both manually and automatically. High correlations were found for all types of measurement: r = 0.993 for velocity measurements, r = 0.995 for time interval measurements, r = 0.881 for acceleration measurements, r = 0.867 for pressure half-time measurements, and r = 0.993 for flow integral measurements. When compared with manual measurements, automatized measurements displayed significantly lower intraobserver and interobserver variabilities for all types of measurements. Finally, the automatized measurement system cuts the time spent by a factor of more than five. Such a system of computerized measurements of Doppler flow velocity waveforms should become increasingly valuable as both a clinical and a research tool.

Adult↗
PubMedDate not supplied

[Neutropenia in a patient treated with clozapine in combination with other psychotropic drugs].

Clozapine is an atypical antipsychotic known for its efficacy in refractory schizophrenia. However, according to different epidemiological studies clozapine can induce neutropenia in less than 3% of patients and may represent a major problem for the management of treatment-resistant patients not responding to conventional or other atypical antipsychotics. Recently, a few case of neutropenia have been reported following the addition of other medications to clozapine, notably paroxetine, risperidone, trimethoprim-sulfamethoxazole and erythromycin. In our report we present the case of Mr A., a 40-year-old Caucasian patient with a 20-year history of paranoid schizophrenia. After numerous trials with conventional antipsychotics, partial remission of psychotic symptoms was obtained with clozapine. Over the past eight years during his treatment with clozapine, the patient presented 2 episodes of neutropenia. The first episode came five years after starting clozapine and was attributed to the addition 6 weeks earlier of haloperidol (2 mg/day) to clozapine (250 mg/day) and divalproex (1,500 mg/day). Recently, one week after the addition of risperidone (2 mg/day) to clozapine (550 mg/day), leukocytes count dropped from 12 100/mm(3) to 5 700/mm(3) and neutrophils from 7 400/mm(3) to 900/mm(3). The patient was also taking haloperidol (4 mg/day), methotrimeprazine (35 mg/day), procyclidine (5 mg/day) and valproic acid (1,500 mg/day). Twelve days after discontinuation of risperidone, leukocytes and neutrophils count increased to 11,100/mm(3) and 6,300/mm(3) respectively while the treatment with clozapine was continued. The first eighteen weeks of treatment represent the period where the risk of neutropenia is the highest. In our patient neutropenia occurred 5 and 7 years after starting clozapine. It is proposed that the two neutropenic episode were precipitated by adding respectively haloperidol and risperidone to clozapine. Also, divalproex can potentially cause a decrease in white blood cell count and may have contributed to the two neutropenic episode. It is suggested that drug interactions may be responsible for neutropenia in clozapine treated patients and that clozapine should not necessarily be discontinued in the presence of neutropenia. Also we propose that hematological surveillance should be done on a weekly basis for 4 to 6 weeks following the addition of psychotropic drugs known for their potential to cause neutropenia when associated with clozapine. Therefore polypharmacy may contribute to cause neutropenia in clozapine treated patients and that discontinuation of an antipsychotic should be done before introducing another one.

Adult↗
PubMedDate not supplied

[Diagnosis of myeloid hematologic malignancies: contributions of the 2001 World Health Organization (WHO) classification].

Although the French-American-British (FAB) morphologic classification of myeloid malignancies has been accepted for many years, the important advances in cytogenetic, immunophenotype and genetic fields needed to be integrated in an updated approach using all the available informations. Thus, the World Health Organization (WHO) Classification of haematopoietic malignancies not only incorporates morphology, immunophenotype, cytogenetic and molecular features, but also ensures to be clinically useful. This collaborative project has begun in 1995 and has been published in 2001. The proposed WHO classification is less a disruption with regard to the FAB classification than an updated revision where morphology is always important. These review emphasises the modifications proposed in the new WHO classification concerning the myeloid disorders.

Acute Disease↗
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Cell-mediated and humoral immune responses in chickens infected with Salmonella typhimurium.

The cellular immune responses of leghorn and New Hampshire chickens following oral challenge at 4 weeks of age with Salmonella typhimurium were measured using assays for lymphocyte proliferative responses to mitogens and cytotoxic activity of natural killer (NK) cells. In addition, the humoral immune response to Newcastle disease virus (NDV) vaccine was assessed in S. typhimurium-infected chickens. At 8 and 20 days after infection with S. typhimurium, lymphocyte proliferative responses to various mitogens were significantly higher in S. typhimurium-infected chickens than in uninfected birds of the same breeds. Cytotoxic activity of NK cells was also significantly increased in infected birds on these days. Thirteen days after S. typhimurium infection, infected NDV-vaccinated chickens had higher antibody titers in response to NDV vaccination than uninfected vaccinated birds. NDV titers did not differ among groups at any other time of testing. These results show that both cellular and humoral immune functions are activated in the first 3 weeks following infection of 4-week-old chickens with S. typhimurium.

Animals↗
PubMedDate not supplied

Influence of Marek's disease virus strain AC-1 on cellular immunity in birds carrying endogenous viral genes.

The effects of Marek's disease virus (MDV) strain AC-1 on humoral and cellular immune responses were investigated in two lines of chickens segregating for the endogenous viral (ev) genes ev-6 and ev-12. All birds were vaccinated at 14 days of age against Newcastle disease virus (NDV). At 3 wk of age, 48 birds per line received an intraperitoneal injection of MDV (AC-1 isolate), and 24 were injected with saline. Birds of each group were killed on days 5, 7, 12, and 14 postinfection. Data were first analyzed for each day of testing. Results showed that, for variable measured, treatment effects were similar on days 5 and 7, and on days 12 and 14. Therefore, day 5 and day 7 data, and day 12 and day 14 data were pooled and analyzed. In MDV-infected chickens, proliferative lymphocyte responses to mitogens were suppressed (P < 0.001) after the first and second week of infection, whereas responses to NDV antigen were enhanced (P < 0.001) after the first week and then reduced (P < 0.01) by the end of the second week when compared to uninfected birds. The percentage of CD4+ T cells was higher (P < 0.01), and the percentage of cells expressing major histocompatibility complex (MHC) class II antigens was lower (P < 0.001), in MDV-infected chickens than in uninfected birds. The cytotoxic activity of natural killer (NK) cells was also enhanced (P < 0.001) in MDV-infected birds when compared to uninfected birds. Antibody responses to NDV were not different among groups, and the presence of ev-6 or ev-12 genes did not influence the immune response parameters measured in both infected and uninfected chickens. In conclusion, a marked increase in the CD4+ T lymphocyte population occurred in the early stage of MDV infection in all chickens regardless of the presence of ev genes, whereas the number of cells expressing MHC class II antigen was severely reduced.

Animals↗