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Biomedical subjects

D Bonnet

Publications and source records attributed to D Bonnet.

At least 181 records · Page 10Linked to original sources
PubMed1997

Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice.

The purification of primitive human hematopoietic stem cells has been impaired by the absence of repopulation assays. By using a stringent two-step strategy involving depletion of lineage-positive cells followed by fluorescence-activated cell sorting, we have purified a cell population that is highly enriched for cells capable of multilineage repopulation in nonobese diabetic/severe combined immunodeficient (NOD/SCID) recipients. These SCID-repopulating cells (SRCs) were exclusively found in a cell fraction that expressed high levels of CD34 and no CD38. Through limiting dilution analysis using Poisson statistics, we calculated a frequency of 1 SRC in 617 CD34(+) CD38(-) cells. The highly purified SRC were capable of extensive proliferation in NOD/SCID mice. Mice transplanted with 1 SRC (at limiting cell doses) were able to produce approximately 400, 000 progeny 6 weeks after the transplant. Detailed flow cytometric analysis of the marrow of highly engrafted mice demonstrated both lymphoid and myeloid differentiation, as well as the retention of a significant fraction of CD34(+) CD38(-) cells. These highly purified fractions should be useful for identification of the cellular and molecular mechanisms that regulate primitive human hematopoietic cells. Moreover, the ability to detect and purify primitive cells provides a means to develop conditions for maintaining and/or expanding these cells during in vitro culture.

ADP-ribosyl Cyclase↗
PubMed1997

Atrio-ventricular valve dysplasia in 22 newborn infants.

We retrospectively studied the experience of our institution with isolated dysplasia of one or both atrio-ventricular valves in 22 newborn infants. All patients with associated cardiac malformations were excluded. Ten patients exhibited isolated tricuspid valve dysplasia. One patient had tricuspid valve dysplasia and a dysplastic pulmonary valve. In 10 patients, both atrio-ventricular valves were affected. Finally, mitral valve dysplasia was associated with pulmonary valve stenosis in 1 case. Associated syndromes and/or chromosomal anomalies were: Down syndrome (n=2), trisomy 18 (n=1), Noonan syndrome (n=1), Marfan syndrome (n=3), Ehlers-Danlos and Cutis laxa (n=2). Mortality was 27.2% during follow-up (mean 51 months): 3 patients with chromosomal aneuploidies, 2 patients with severe neonatal Marfan syndrome and 1 with Ehlers-Danlos. Complications were: sustained supra-ventricular tachycardia in 3, neonatal staphylococcal tricuspid valve endocarditis in 1, persistent significant valvular disease in 8. In the remaining 9 survivors, the dysplasia of the atrio-ventricular valves persists with absent or mild incompetence. Beside obvious chromosomal anomalies, newborn infants with dysplastic valves should be investigated for manifestations of connective tissue disorders. This may help to identify new pleiotropic syndromes which include valvular dysplasia as one manifestation.

Aneuploidy↗
PubMed1997

Microsatellite DNA markers detects 95% of chromosome 22q11 deletions.

Cono-truncal cardiac malformations account for some 50% of congenital heart defects in newborn infants. Recently, hemizygosity for chromosome 22q11.2 was reported in patients with the DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) and causally related disorders. We have explored the potential use of microsatellite DNA markers for rapid detection of 22q11 deletions in 19 newborn infants referred for cono-truncal heart malformations with associated DGS/VCFS anomalies. A failure of parental inheritance was documented in 84.2% of cases (16/19). PCR-based genotyping using microsatellite DNA markers located within the commonly deleted region allowed us either to confirm or reject a 22q11 microdeletion in 94.3% of cases (18/19) within 24 hours. This test is now currently performed in the infants referred to us for a cono-truncal heart malformation as a first intention screening for 22q11 microdeletion.

Alleles↗
PubMed1997

Progressive left main coronary artery obstruction leading to myocardial infarction in a child with Williams syndrome.

UNLABELLED: We report a 3-year-old child with Williams syndrome in whom the first vascular feature of the syndrome was a myocardial infarction related to the occlusion of the left main coronary artery trunk. This coronary artery occlusion was not associated with supravalvular aortic stenosis. CONCLUSION: This report emphazises that acute vascular events related to systemic artery anomalies may reveal Williams syndrome.

Child, Preschool↗
PubMed1997

Coronary artery obstruction after the arterial switch operation for transposition of the great arteries in newborns.

OBJECTIVES: We sought to describe a large series of coronary artery obstructions after the arterial switch operation for transposition of the great arteries and to discuss their clinical implications. BACKGROUND: Aortic root angiography and myocardial perfusion imaging yield ambiguous results regarding the fate of the coronary artery anastomoses after the arterial switch operation. Late death related to coronary artery obstruction and growth of the translocated coronary arteries are of major concern in these patients. METHODS: Selective coronary artery angiography was performed prospectively in a total of 165 children. RESULTS: A total of 12 coronary occlusions, 8 major stenoses, 6 minor stenoses of the left ostium and 4 stretchings of one coronary artery were identified. Obstructions were more frequent in types D and E (p < 0.001) of the Yacoub and Radley-Smith classification. Coronary obstruction was documented in all patients with electrocardiographic and ultrasound evidence of myocardial ischemia at time of study. Early postoperative ischemia did not predict coronary artery lesion if the patient had fully recovered. Persistent or delayed myocardial ischemia was highly predictive of coronary artery lesions. The incidence of coronary artery obstruction was very high (11 of 35) in patients operated on by a rapidly abandoned technique of single-orifice reimplantation of both coronary artery ostia. CONCLUSIONS: Selective coronary angiography is the most accurate means to assess coronary artery obstruction after the arterial switch operation. Precise diagnosis of coronary artery lesions after this operation will help to elucidate the pathogenesis, develop adequate therapeutic strategies and might indicate how to prevent coronary complications after operation.

Child, Preschool↗
PubMed1997

Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.

Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.

Abnormalities, Multiple↗
PubMed1997

Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.

On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.

ADP-ribosyl Cyclase↗
PubMed1997

Features of DiGeorge syndrome and CHARGE association in five patients.

We report on five patients presenting with features of two congenital disorders, DiGeorge syndrome (DGS) and CHARGE association. CHARGE association is usually sporadic and its origin is as yet unknown. Conversely, more than 90% of DGS patients are monosomic for the 22q11.2 chromosomal region. In each of the five patients, both cytogenetic and molecular analysis for the 22q11.2 region were normal. In view of the broad clinical spectrum and the likely genetic heterogeneity of both disorders, these cases are consistent with the extended phenotype of either DGS without 22q11.2 deletion or CHARGE association, especially as several features of CHARGE association have been reported in rare patients with 22q11.2 deletion association phenotypes. On the other hand, these could be novel cases of an independent association involving a complex defect of neural crest cells originating from the pharyngeal pouches.

Abnormalities, Multiple↗
PubMed1997

[Benign mediastinal opacity: Castleman disease, apropos of a case and review of the current literature].

We report a case of fortuitously observed Castleman's disease. An mediastinal opacity was observed on the chest x-ray. At surgery, the apparently benign tumor was well individualized. Pathology reported Castleman's disease. Pathogenesis is unknown. Recent data on localized and more diffuse forms of this disease are presented. Diffuse forms occur more readily in immunodepressed patients.

Adult↗
PubMed1997

[Malaria attack: a very late relapse due to Plasmodium vivax].

Plasmodium vivax malaria late-forms rarely exceed two years--the authors reported a late-form more than twenty years after a stay in endemic area. This late-form occurred in an immunocompromised patient with two terminal-stage neoplasia receiving radio, chimio corticotherapy associated with anemia and thrombopenia. Repeated-tests allowed the diagnostic.

Adenocarcinoma↗
PubMed1997

[Congenital coronary-cardiac fistula in children. Effects of surgical occlusion and percutaneous embolization].

Twenty-four children aged 2 months to 8 years (average: 3 years) with congenital coronary artery fistulae were studied. In 20 cases, the fistula presented with a continuous murmur: in 4 cases, pulmonary flow was increased to such an extent that it led to cardiac failure. Echocardiography and coronary angiography showed that the fistula originated from the left coronary artery or one of its branches in 13 cases and from the right coronary artery in 11 cases. All but one fistula, which drained into the left atrial appendage, drained into the right heart chambers (ventricle: 14 cases; atrium: 9 cases). Spontaneous regression after 9 years was observed in 1 case. The other children were treated: by surgery in 20 cases (1 external ligature and 19 open heart occlusions) with 2 residual shunts (including the case ligated) which had to be reoperated. Three children underwent percutaneous embolisation resulting in 1 failure and 2 successes. After an average follow-up of 6.5 years (5 months to 15.5 years), all patients were alive and doing well with normal resting and exercise ECGs, normal Thallium scintigraphy (5 cases) and normal left ventricular function on echocardiography. Selective control coronary angiography (14 cases) showed a reduction in fistula diameter from 10 +/- 3.7 to 4.5 +/- 1.2 mm (p < 0.0001). The authors conclude that all congenital coronary fistulae should be occluded, by percutaneous embolisation when the anatomical features are favourable. The other cases require surgical occlusion, the long-term results of which are very good.

Cardiac Surgical Procedures↗
PubMed1997

[Double discordances with ventricular septal defect and pulmonary obstruction. A study of 72 cases].

Seventy-two patients with corrected transposition of the great arteries with ventricular septal defect and pulmonary obstruction were studied. Four deaths occurred in the neonatal period and two were lost to follow-up. The remaining 66 were divided into three groups: 1) Eight patients were not operated on because the lesions were well compensated; they are all alive and doing well eight years later. 2) Thirty-eight patients were treated with palliative surgery: one or more systemico-pulmonary shunts (33 cases), total cavo-pulmonary connection (1 case) and partial cavo-pulmonary connection complementary to a shunt (4 cases). There were 3 deaths and 17 patients were lost to follow-up. However, the 18 survivors are all well seven years later. 3) The other 20 patients underwent surgery for severe hypoxia, after previous shunt in 18 cases. A conventional surgical protocol was respected in 17 cases (closure of ventricular septal defect with pulmonary disobstruction by a direct pulmonary plasty or by ventriculo-pulmonary conduit). There were 4 deaths, 2 tricuspid valve replacements, 5 complete atrioventricular blocks requiring permanent pacing, 5 lost to follow-up and 8 good results after 4 years follow-up. In the last 3 cases, "anatomical" correction was attempted by tunnelling of the left ventricle to the aorta, conduit from the right ventricule to the pulmonary artery and intra-atrial Mustard procedure: these 3 children are doing well after 1 year though one of them required permanent pacing. Therefore, there is no place for elective surgery in this malformation: when necessary, the best option is to remain palliative as long as possible: when correction is required, an anatomical correction is the best procedure.

Cardiac Surgical Procedures↗
PubMed1997

[Non-surgical ventricular training before arterial switch. Focus on an animal model in lambs].

One of the conditions for successful anatomical correction of transposition of the great arteries (arterial switch) or of double discordance (double switch) is the ability of the subpulmonary left ventricle to adapt to the systemic circulation when restored to its subaortic position. A balloon catheter designed for training the subpulmonary ventricle by progressive occlusion of the main pulmonary artery (NuMed) was implanted in six lambs aged 45 days and inflated progressively to obtain the maximum tolerated right ventricular pressure. Six controls were instrumented without balloon inflation. The experiment lasted 5 days. Progressive inflation of the balloon to a right ventricular pressure > 70% of the systemic (carotid) pressure led to bradycardia with venous desaturation and acidosis which regressed when the balloon was deflated. In one animal, progressive adjustment enabled a right ventricular pressure of 75% of the systemic pressure to be obtained throughout the last day of the study. No significant right ventricular hypertrophy was obtained. The value of this technique is in assessing the afterload reserve of the tested ventricle before surgical banding of the pulmonary artery, the first step to anatomical correction for restoration of concordance of double discordance or of transposition of the great arteries previously treated by a Senning or Mustard procedure.

Animals↗
PubMed1997

[Aortic-ventricular tunnel with right coronary artery atresia].

An aortico-left ventricular tunnel was diagnosed at echocardiography in a 6 week old baby after fortuitous detection of a systolic and diastolic murmur. Its association with atresia of the right coronary ostium, suspected at echocardiogoraphy, was confirmed at surgery which included occlusion of the tunnel orifices, aortic commissurotomy and reimplantation of the right coronary artery. The short-term postoperative result is excellent. This is an exceptional malformation, the clinical diagnosis of which is relatively easy. Its relationship with the right coronary artery conforms to an embryological logic and must be investigated thoroughly before surgery to avoid compromising myocardial revascularisation.

Aorta, Thoracic↗
PubMed1997

[Contribution of genetics to pathogenicity and diagnosis of Marfan syndrome].

The anatomical substrate of Marfan's syndrome is a degeneration of elastic fibres and disorganization of the collagen. It is now known that these lesions are due to mutation of genes localised on chromosome 15. The first of them (FBN1) codes for the main constitutive protein of the elastic tissue: fibrillin 1, present mainly in structures which must resist load and stress (aortic adventitia, the suspending ligament of the lens, skin); the second (FBN2) codes for fibrillin 2: responsible for the orientation of the elastin and mainly present in cartilage, the aortic media, the bronchi, and all tissues rich in elastin. Mutations of FBN1 are very common and are associated not only with Marfan's syndrome but also fibrillinopathies: incomplete forms, neonatal forms, ectopic lens, isolated aneurysms of the thoracic aorta. The widespread distribution of fibrillin explains the pleiotropic nature of Marfan's syndrome and its clinical presentation. The variability of interfamilial expression is due to genetic heterogeneity (at least two genes) and alletic differences (different mutations of FBN1 from one family to another), also explaining mild forms due to quantitative reduction in normal fibrillin and severe forms by "negative dominance" where the fibrillin is structurally abnormal because of alteration of the polymerisation mechanism. The biologic diagnosis of fibrillopathy can be made by a protein test analysing fibrillin on a culture of the patient's fibroblast obtained by skin biopsy. At present, molecular diagnosis of the mutation within the FBN1 gene is not feasible as a routine procedure.

Abnormalities, Multiple↗
PubMed1997

[Travel and chronic respiratory insufficiency].

Changes in climate, altitude and lifestyle during travel confronts patients presenting chronic respiratory insufficiency with special problems. A major challenge is related to high altitude during air travel. To limit risks, a preflight examination is necessary to ascertain respiratory status. Patients requiring oxygen therapy must ensure availability both during the flight and at the destination. Patients with asthma or chronic bronchitis must bring along a sufficient supply of usual inhalers. All patients should carry a doctor's letter describing their condition and listing medications. Using these elementary precautions, patients with chronic respiratory insufficiency can safely enjoy sightseeing and outdoor leisure activities.

Altitude↗