Intractable diarrhoea of infancy caused by neutrophil specific granule deficiency and cured by stem cell transplantation.
Explore the source record for details and available documents.
Cytoplasmic Granules↗
Biomedical subjects
M Gharib
Publications and source records attributed to M Gharib.
Flow in the early embryonic human heart: a numerical study.
Computational fluid dynamic (CFD) experimentation provides a unique medium for detailed examination of flow through complex embryonic heart structures. The purpose of this investigation was to demonstrate that streaming blood flow patterns exist in the early embryonic heart and that fluid surface stresses change significantly with anomalous alterations in fetal heart lumen shape. Stages 10 and 11 early human embryo hearts were digitized as calibrated two-dimensional (2D) cross-sectional sequential images. A 3D surface was constructed from the stacking of these 2D images. CFD flow solutions were obtained (steady and pulsatile flow). Particle traces were placed in the inlet and outlet portions of these two stages. Sections of the embryonic heart were artificially reshaped. CFD flow solutions were obtained and surface stress changes analyzed. Streaming was shown to exist, with particles released on one or the other side of the cardiac lumen tending not to cross over and mix with particles released from the opposite side of the cardiac lumen. Shear stress changes (stage 10) occur in the altered lumens. Streaming exists in steady and pulsatile flow scenarios in the embryonic heart models. There are differences in local shear stress distributions with surface shape anomalies of the fetal heart lumen. These observations may help shed light on the potential role of fluid dynamic factors in determining patterns of abnormal heart development.
Blood Flow Velocity↗
[Management of the bank of biological material in the hospital-based SEROCO and HEMOCO cohorts of HIV-infected patients].
The French SEROCO and HEMOCO hospital-based cohorts have enrolled and followed HIV-infected patients, before and after the highly active antiretroviral therapy era. Among the objectives in 1988, was explicitly mentioned the constitution of a centralised bank of biological material (serums at enrollment and every 6 months, PBMC at enrollment and every 18 months). This paper details the organisation of the bank and the numerous studies performed from this bank, and presents a few simple decision rules which have been developed with the growing acquired experience.
Antiretroviral Therapy, Highly Active↗
The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart.
The Gordian knot of anatomy has been the architectural arrangement of ventricular muscle mass, which may have finally become understood. The description of Francisco Torrent-Guasp's model of the helical heart is presented, which includes the cardiac structures that produce 2 simple loops that start at the pulmonary artery and end in the aorta. An unscrolled ventricular band is shown, achieved by blunt dissection that extends between the points of origin of the right ventricle, at the pulmonary artery root, to termination at the aortic root, in the left ventricle. These components include a spiral horizontal basal loop that surrounds the right and left ventricular cavities, and changes direction to cause a second spiral, produced by almost vertically oriented fibers, giving rise to the helical configuration of the ventricular myocardial band. These anatomic structures are successively activated, as with a peristaltic wave, starting at the right ventricle (just below the pulmonary artery) and progressing toward the aorta to produce a sequence of narrowing, caused by the basal loop contraction, shortening (related predominantly to the descendant segment contraction), lengthening (produced by the ascendant segment contraction), and widening, as a consequence of several factors that act during ventricular myocardium relaxation. These sequences control the ventricular events responsible for ejection to empty and suction to fill. These mechanical interactions of structure and function are defined in relation to chronologic location of the successive cardiac functional events in the aortic, left ventricular, and left atrial recordings.
Animals↗
The structure and function of the helical heart and its buttress wrapping. III. The electric spiral of the heart: The hypothesis of the anisotropic conducting matrix.
The study of the dissemination of the electric impulse throughout the ventricular myocardium, which gave rise to the current theories, was performed without taking into consideration the complex architecture of the cardiac muscle elucidated by more recent researchers. We propose a novel hypothesis based on the special macroscopic structure of the heart, the anisotropic electric and mechanical behavior of the myocardium, the characteristics of the intercellular matrix and its very special collagen scaffolding, chemical composition, and biochemistry. The unique properties of the intercellular matrix would make it especially suited to function, in conjunction with the specialized conducting system (His-Purkinje system), as an efficient anisotropic conductor for the spread of electric activation in the heart, and to allow an optimal sequence of excitation-contraction coupling that results in the coordination of effective myocardial contraction in birds and mammals of the most varied known heart rates.
Animals↗
The structure and function of the helical heart and its buttress wrapping. IV. Concepts of dynamic function from the normal macroscopic helical structure.
Torrent-Guasp's model of the helical heart is presented, which includes the cardiac muscular structures that produce 2 simple loops and that start at the pulmonary artery and end in the aorta. These components include a horizontal basal loop that surrounds the right and left ventricles, changes direction through a spiral fold in the ventricular band to cause a ventricular helix produced by now obliquely oriented fibers, forming a descending and ascending segment of the apical loop with an apical vortex. These anatomic concepts are successively activated to produce a sequence of narrowing by the basal loop, shortening by the descending segment, lengthening by the ascending segment, and widening in the cardiac cycle that causes ventricular ejection to empty and suction to fill. The factors responsible for internal torsional movements for cardiac output and suction are defined, together with mechanisms responsible for electromechanical activity produced during sequential changes in contraction and relaxation properties. These interactions of mechanical structure and function are defined in relation to pressure-related cardiac events observed from aortic, left ventricular, and left atrial recordings.
Animals↗
Optimizing ventricular shape in anterior restoration.
Ishemic dilated cardiomyopathy results from altered muscle mechanics. Ventricular restoration is aimed at altering the volume and shape changes that follow myocardial infarction. Optimal surgical methods to achieve this goal are not well defined, but it has been shown that sphericity is an important determinant of long-term outcome. We present the rationale and techniques for returning the globular remodeled ventricle to a more elliptical shape. Clinical data from our RESTORE registry does not suggest an improvement in early or late mortality with such methods but opens the way for late evaluation of functional and exercise capacity.
Cardiovascular Surgical Procedures↗
A stepwise approach to the treatment of early onset nephrotic syndrome.
We have retrospectively reviewed our single-center experience of the treatment of early onset nephrotic syndrome (NS). From 1991 to 1998, ten children with NS were treated. Kidney biopsy showed focal sclerosis (n=1), diffuse mesangial sclerosis (n=7), and congenital NS of the Finnish type (n=2). Associated conditions included incomplete Drash syndrome (n=1), Galloway-Mowat syndrome (n=1), and severe mental and motor retardation of unknown origin (n=3). From 1991 to 1997, five children with NS were treated. Bilateral nephrectomy (NX) was performed in three, one patient with severe retardation died at 4 years and NX was not performed in one patient who showed satisfactory growth and development. Three of these children were dialyzed and two were successfully transplanted. One patient was transplanted without previous dialysis. From 1997 to 1998, five children were treated with a regimen that included captopril and indomethacin (CAPTO/INDO). CAPTO/ INDO was successful in increasing serum protein in all patients and producing growth and development in four patients. In two patients CAPTO/INDO was successful only after unilateral NX. Our experience indicates that CAPTO/INDO may be a valuable treatment in patients with early onset NS. An individualized stepwise approach including unilateral NX should be considered to achieve optimal results.
Age of Onset↗
Vortex shedding as a mechanism for free emboli formation in mechanical heart valves.
The high incidence of thromboembolic complications of mechanical heart valves (MHV) limits their success as permanent implants. The thrombogenicity of all MHV is primarily due to platelet activation by contact with foreign surfaces and by nonphysiological flow patterns. The latter include elevated flow stresses and regions of recirculation of blood that are induced by valve design characteristics. A numerical simulation of unsteady turbulent flow through a bileaflet MHV was conducted, using the Wilcox k-omega turbulence model for internal low-Reynolds-number flows, and compared to quantitative flow visualization performed in a pulse duplicator system using Digital Particle Image Velocimetry (DPIV). The wake of the valve leaflet during the deceleration phase revealed an intricate pattern of interacting shed vortices. Particle paths showed that platelets that were exposed to the highest flow stresses around the leaflets were entrapped within the shed vortices. Potentially activated, such platelets may tend to aggregate and form free emboli. Once formed, such free emboli would be convected downstream by the shed vortices, increasing the risk of systemic emboli.
Biomedical Engineering↗
Accuracy of Doppler methods for estimating peak-to-peak and peak instantaneous gradients across coarctation of the aorta: An In vitro study.
Although data exist that address the attempt to correlate noninvasive Doppler-derived pressure gradients with invasive catheter pressure gradients in patients with coarctation of the aorta, few data exist about stiffness of the proximal descending aorta (precoarctation) and its relation to these pressure measurements. In this study, an in vitro flow model of a simulated neonatal aorta with a coarctation was developed. Three proximal descending aortas of different stiffnesses were used. The stiffness index of the proximal descending aorta was calculated as beta = ln [systolic pressure/diastolic pressure/(systolic diameter - diastolic diameter)]. We evaluated pressure gradients obtained by continuous wave Doppler and standard catheter methods and looked at acceleration of flow velocity determined by pulsed wave Doppler in the 3 precoarctation segments of differing stiffnesses. Pressures in the proximal descending aorta (precoarctation) increased with increasing stiffness, ranging from 105 mm Hg (soft) to greater than 300 mm Hg (stiff). Continuous wave Doppler instantaneous pressure gradients overestimated the catheter instantaneous pressure gradients substantially (mean 41% +/- 19%). The stiffer the precoarctation segment, the more the degree of overestimation: soft, 0% to 63% (= 3.47); medium, 13% to 54% (beta = 4.42); and stiff, 43% to 66% (beta = 5.91). Inclusion of the precoarctation velocity [V1] component in the Bernoulli equation did not significantly improve the correlation or the agreement. An additional observation was that pullback catheter peak-to-peak gradients were higher than simultaneous peak-to-peak gradients. In the stiff aorta, this difference could be greater than 22 mm Hg (>19%). Acceleration of flow velocity toward the coarctation was evident by pulsed wave Doppler interrogation. Increasing the stiffness of the precoarctation segment also increased the degree of acceleration within this proximal segment: soft, 0.4 to 0.8 m/s; medium, 0.5 to 1. 4 m/s; and stiff, 0.7 to 1.5 m/s. These data suggest that increasing stiffness of the proximal descending aorta can alter the continuous wave detected Doppler gradient and although the gradient itself has increased, it may not predict accurately the true severity of the localized, most severely obstructed segment.
Aorta↗
Evaluation of descending aortic flow volumes and effective orifice area through aortic coarctation by spatiotemporal integration of color Doppler data: An in vitro study.
Flow volumes in an in vitro model of the aorta with 3 different degrees of stiffness (stiff, moderately stiff, and compliant) proximal to a coarctation were calculated by using a digital color Doppler echocardiography flow calculation method that semiautomatically integrates spatial and temporal color flow velocity data. These flow volumes were compared with those obtained by the conventional pulsed Doppler method with reference to ultrasonic flowmeter. Flow volumes determined by the automated method agreed well with those obtained by ultrasonic flowmeter, even in this compliant aorta model with vessel size changing with pulsation, whereas the pulsed Doppler method overestimated the reference data, especially for more compliant descending aortic segments. The combination of flow data with continuous wave Doppler allows definition of effective orifice area for coarctation.
Aorta↗
Microbubbles and mitral valve prostheses - transesophageal echocardiographic evaluation.
OBJECTIVE: To assess whether microbubbles are associated with a specific type of mitral valve prosthesis and to investigate the relationship of microbubbles to ventricular function and mitral regurgitation. One of the types of spontaneous echocardiographic contrast observed in patients with prosthetic heart valves has been described as microbubbles. METHODS: Clinical data and videotapes of patients with a prosthetic mitral valve who had undergone transesophageal echocardiography at the UCLA Medical Center between May 1989 and February 1995 were retrospectively reviewed. There were 109 studies (74 patients) available for review by two independent observers. RESULTS: Microbubbles occurred in 49 of the 66 studies of St. Jude valves ( 74%), eight of the 12 studies of Bjork Shiley valves (67%), four of four studies of Medtronic valves (100%) and zero of 23 studies of tissue valves (0%). Patients with an estimated ejection fraction greater than 45% were found to have a much higher likelihood of having microbubbles observed. There was no statistically significant association between the degree of mitral regurgitation and the observation of microbubbles. CONCLUSIONS: Microbubbles are a common phenomenon occurring in patients with mechanical mitral prostheses compared with tissue mitral valve prostheses. Their formation depends on the systolic ventricular function, suggesting a cavitation-like phenomenon participating in their formation perhaps due to the rate or velocity of the valve closure.
Adolescent↗
A complex, high cloacal malformation: case report.
Cloacal malformations are rare, complex inhibitional anomalies of early embryogenesis. We report a patient with a cloacal malformation in which a septate vagina and a rectal fistula emptied through a common orifice onto an exstrophic bladder plate. Additional anomalies included an omphalocele and malformations of the upper urinary tract and the lower extremities, skeleton, and vertebral column.
Abnormalities, Multiple↗
Interactions of lymphokine-activated killer cells and A549 lung carcinoma nodules maintained in three-dimensional culture.
Lymphokine-activated killer (LAK) cells were cocultured in the presence of interleukin-2 (IL-2), with pulmonary surfactant secreting A549 lung carcinoma nodules and maintained in continuous three-dimensional culture for 2-6 days in an attempt to test the response of tumor cells which produce LAK cell inhibitory substances. The A549 nodules secrete mucus which envelops them. This mucus is also secreted inside pseudoalveolar structures characteristic of these nodules. The mucus contains the pulmonary surfactant and sialomucins, both LAK cell inhibitory substances. The spontaneous infiltration into the neoplastic tissue and the membrane contacts established between the two cell types were studied by means of histological, immunohistochemical and electron-microscopic methods. Free-floating LAK cells were allowed to sediment and adhere freely to the nodule surface. The cytostatic and cytolytic effects of LAK cells were tested using thymidine incorporation into DNA and flow cytometry. Despite the presence of a mucus envelope, LAK cells adhered to the A549 nodule surface and penetrated spontaneously into them in the presence of IL-2; they settled mainly in the pseudoalveolar structures where they became apoptotic. According to electron-microscopic observations performed on the second day of coculture, the LAK cells, which remained between the cancer cells, established mostly pinpoint contacts with the carcinoma cells, forming cytoplasmic fusions. These fusions indicate the induction of pores in both the cancer cell and the LAK cell membranes. Electron-microscopic observation also displayed LAK-cell-associated apoptotic and necrotic carcinoma cells. However, at this stage of the coculture (day 2), the DNA synthesis rate of the A549 nodules still remained unchanged; it diminished by approximately 3 times on day 4 and almost stopped on day 6: nodule disintegration was then complete. In the free-floating LAK cell component of the cocultures, DNA synthesis was already strongly inhibited (26x) by the second day. Nevertheless, their cytolytic effect remained unaltered, as was tested on A549 monolayer cells. The presence of tumor necrosis factor (TNF) in the coculture supernatant has been demonstrated, and when coculturing took place in the presence of monoclonal TNF antibody, nodule proliferation was significantly enhanced (up to 145%). Our results indicate that, despite the presence of pulmonary surfactant and sialomucins containing mucus, LAK cells were capable of killing lung carcinoma cells in three-dimensional culture at an early stage of coculture (day 2) by direct cell-to-cell contact. Total nodule disintegration, however, was complete much later (on day 6), and taking into account the low amount of LAK cells in the cancer tissue, this seemed to be the result of an indirect effect implying, in particular, the presence of soluble TNF.
Apoptosis↗
Current status of flow convergence for clinical applications: is it a leaning tower of "PISA"?
Spatial appreciation of flow velocities using Doppler color flow mapping has led to quantitative evaluation of the zone of flow convergence proximal to a regurgitant orifice. Based on the theory of conservation of mass, geometric analysis, assuming a series of hemispheric shells of increasing velocity as flow converges on the orifice--the so-called proximal isovelocity surface area (PISA) effect--has yielded methods promising noninvasive measurement of regurgitant flow rate. When combined with conventional Doppler ultrasound to measure orifice velocity, regurgitant orifice area, the major predictor of regurgitation severity, can also be estimated. The high temporal resolution of color M-mode can be used to evaluate dynamic changes in orifice area, as seen in many pathologic conditions, which enhances our appreciation of the pathophysiology of regurgitation. The PISA methodology is potentially applicable to any restrictive orifice and has gained some credibility in the quantitative evaluation of other valve pathology, particularly mitral and tricuspid regurgitation, and in congenital heart disease. Although the current limitations of PISA estimates of regurgitation have tempered its introduction as a valuable clinical tool, considerable efforts in in vitro and clinical research have improved our understanding of the problems and limitations of the PISA methodology and provided a firm platform for continuing research into the accurate quantitative assessment of valve regurgitation and the expanding clinical role of quantitative Doppler color flow mapping.
Blood Flow Velocity↗
Three-dimensional reconstruction of color Doppler flow convergence regions and regurgitant jets: an in vitro quantitative study.
OBJECTIVES: This study sought to investigate the applicability of a current implementation of a three-dimensional echocardiographic reconstruction method for color Doppler flow convergence and regurgitant jet imaging. BACKGROUND: Evaluation of regurgitant flow events, such as flow convergences or regurgitant jets, using two-dimensional imaging ultrasound color flow Doppler systems may not be robust enough to characterize these spatially complex events. METHODS: We studied two in vitro models using steady flow to optimize results. In the first constant-flow model, two different orifices were each mounted to produce flow convergences and free jets--a circular orifice and a rectangular orifice with orifice area of 0.24 cm(2). In another flow model, steady flows through a circular orifice were directed toward a curved surrounding wall to produce wall adherent jets. Video composite data of color Doppler flow images from both free jet and wall jet models were reconstructed and analyzed after computer-controlled 180 degrees rotational acquisition using a TomTec computer. RESULTS: For the free jet model there was an excellent relation between actual flow rates and three-dimensional regurgitant jet volumes for both circular and rectangular orifices (r = 0.99 and r = 0.98, respectively). However, the rectangular orifice produced larger jet volumes than the circular orifice, even at the same flow rates (p < 0.0001). Calculated flow rates by the hemispheric model using one axial measurement of the flow convergence isovelocity surface from two-dimensional color flow images underestimated actual flow rate by 35% for the circular orifice and by 44% for the rectangular orifice, whereas a hemielliptic method implemented using three axial measurements of the flow convergence zone derived using three-dimensional reconstruction correlated well with and underestimated actual flow rate to a lesser degree (22% for the circular orifice, 32% for the rectangular orifice). In the wall jet model, the jets were flattened against and spread along the wall and had reduced regurgitant jet volumes compared with free jets (p < 0.01). CONCLUSIONS: Three-dimensional reconstruction of flow imaged by color Doppler may add quantitative spatial information to aid computation methods that have been used for evaluating valvular regurgitation, especially where they related to complex geometric flow events.
Echocardiography, Doppler, Color↗
Nature of flow acceleration into a finite-sized orifice: steady and pulsatile flow studies on the flow convergence region using simultaneous ultrasound Doppler flow mapping and laser Doppler velocimetry.
OBJECTIVES: This study investigated the proximal centerline flow convergence region simultaneously by both color Doppler and laser Doppler velocimetry. BACKGROUND: Although numerous investigations have been performed to test the flow convergence method, to our knowledge there has yet been no experimental study using reference standard velocimetric techniques to define precisely the hydrodynamic factors involved in the accelerating flow region during steady and pulsatile flow. METHODS: Using an in vitro model that allows velocity measurements by laser Doppler velocimetry with simultaneous comparison with color Doppler results, we studied the centerline flow acceleration region proximal to orifices of various sizes (0.08 to 2.0 cm2). RESULTS: Agreement between theory and experimental velocities was good for large flow rates through small orifices only, and only at distances > 1.2 cm from the orifice. Changing the orifice shape from circular to slitlike produced no significant changes in velocity profiles. Constraining the proximal side walls caused a significant increase in proximal velocities at distances > 0.7 cm for the largest orifice only (2.0 cm2). Calculated flow rates agreed well with actual flow rates, with functional dependence on proximal distance and orifice size. Velocity profiles for pulsatile flow were similar to steady state flow profiles and could be integrated to calculate stroke volumes, which followed actual flow volumes well, although with general overestimation (y = 1.22x + 0.164, r = 0.92), most likely due to the use of all available proximal velocities. CONCLUSIONS: The accelerating proximal flow region responds to several hydrodynamic factors that can affect flow quantitation using the flow convergence method in the clinical situation.
Blood Flow Velocity↗
Long-term functional results and quality of life after colon interposition for long-gap oesophageal atresia.
Out of a series of 146 patients with oesophageal atresia 9 (6.2%) underwent colon interposition from 1963 to 1971. All eight surviving patients were seen at follow-up after a mean of 22 years. Three patients were free of specific symptoms according to the criteria of DeMeester, two had moderate and three severe distress. The mean time for consuming a standardized test meal was 15 minutes, compared to 8 minutes in healthy controls. Patients required 1-9 minutes to transport liquid barium through the transplant, compared to < 10 seconds in control subjects. Histological evaluation revealed a normal architecture of the colonic and ileal epithelium in three patients who underwent endoscopy. In none of these patients were contractions in the colon graft related to the act of swallowing recorded on manometry. Unimpaired quality of life was indicated by the Spitzer index which scored a mean of nine out of ten points. However, on a 100point visual analogue scale patients scored their global quality of life 66 and the mean Gastrointestinal Quality of Life Index was 92.2, compared to 107.6 in healthy control subjects (p < 0.05). This impairment was exclusively due to specific symptoms which scored 49.3 in patients and 59 in healthy individuals (p < 0.05). Physical and social functions, emotions, and inconvenience of a medical treatment were similar to control subjects. We conclude that colon interposition for long-gap oesophageal atresia achieves acceptable long-term functional results. However, specific symptoms lead to a considerable impairment in quality of life.
Adult↗