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Biomedical subjects

M Abboud

Publications and source records attributed to M Abboud.

At least 19 recordsLinked to original sources

3D reconstruction of dental specimens from 2D histological images and microCT-scans.

Direct comparison of experimental and theoretical results in biomechanical studies requires a careful reconstruction of specimen surfaces to achieve a satisfactory congruence for validation. In this paper a semi-automatic approach is described to reconstruct triangular boundary representations from images originating from, either histological sections or microCT-, CT- or MRI-data, respectively. In a user-guided first step, planar 2D contours were extracted for every material of interest, using image segmentation techniques. In a second step, standard 2D triangulation algorithms were used to derive high quality mesh representations of the underlying surfaces. This was accomplished by converting the 2D meshes into 3D meshes by a novel lifting procedure. The meshes can be imported as is into finite element programme packages such as Marc/Mentat or COSMOS/M. Accuracy and feasibility of the algorithm is demonstrated by reconstructing several specimens as examples and comparing simulated results with available measurements performed on the original objects.

Algorithms↗

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Adolescent↗

Neuronal synthesized insulin roles on neural differentiation within fetal rat neuron cell cultures.

We previously, described the production and secretion of insulin by fetal neurons in culture and demonstrated that neuronal synthesized insulin [I(n)] promoted neurofilament distribution and axonal growth. In this study we investigated the role of I(n) in promoting neural differentiation. Stem cells from 16 day gestational age rat brains were cultured in an insulin-free defined medium (IFDM) and treated with: 5, 20 or 100 ng/ml of exogenous insulin, 100 ng/ml insulin-like growth factor I (IGF-I) or an anti-insulin antibody. The neurons were studied at 1 and 3 days of incubation. The total number of cells showed no significant difference (P>0.05) in any of the media used, except the IFDM at day 3 of incubation treated with the anti-insulin antibody (P<0.05) and IGF-I to 20 ng/ml of insulin (P<0.05). No significant difference (P>0.05) was found in the number of differentiated neurons incubated in the IFMD, in which the neurons produce and secrete I(n), between days 1 and 3 of incubation, but neural differentiation decreased significantly (P<0.05) when treated with the anti-insulin antibody. Exogenous insulin significantly increased (P<0.05) the number of differentiated neurons compared to the IFDM. A significant reduction (P<0.05) of differentiated neurons was observed at day 3 of incubation with IGF-I compared to all the different media. Thus, I(n) has a role in promoting neural differentiation and growth, but exogenous insulin promoted neural differentiation and growth beyond I(n).

Animals↗

Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial (STOP) in sickle-cell anemia.

OBJECTIVE: The Stroke Prevention Trial (STOP) demonstrated that chronic transfusion is highly effective in reducing the risk of stroke in children with sickle-cell disease and an abnormal transcranial Doppler ultrasonography examination result. Our objective was to determine whether chronic transfusion therapy reduces the incidence of pain and acute chest syndrome. METHODS: During STOP, 130 children with sickle-cell anemia or sickle beta(0)-thalassemia and abnormal transcranial Doppler ultrasonography examination result were randomly assigned to chronic transfusion (n = 63) or observation (n = 67). In addition to monitoring for stroke, nonneurologic sickle-cell complications were identified and recorded. RESULTS: Mean age at STOP study entry was 8.3 +/- 3.3 years, and mean follow-up was 19.6 +/- 6.5 months. Hospitalization rates (based on intent-to-treat analysis) for acute chest syndrome were 4.8 and 15.3 per 100 patient-years (P =.0027) and for pain were 16.2 and 27.6 per 100 patient-years (P =.13) in the chronic transfusion and observed groups, respectively. If analyzed according to treatment actually received, the difference in pain rate becomes significant (9.7 vs 27.1 events per 100 patient-years, P =.014), and transfusion remains protective from acute chest syndrome (2.2 vs 15.7 events per 100 patient-years, P =.0001). CONCLUSIONS: Compliance with aggressive chronic transfusion reduces the frequency of acute chest syndrome and pain episodes.

Adolescent↗

PMMA-based composite materials with reactive ceramic fillers: IV. Radiopacifying particles embedded in PMMA beads for acrylic bone cements.

New acrylic bone cements were prepared from alumina particles previously treated by 3-(trimethoxysilyl)propylmethacrylate (gamma-MPS) and embedded in poly(methylmethacrylate-co-ethylacrylate) beads with about 7 mol% of ethyl acrylate repeating units. The encapsulation was performed through a conventional suspension polymerization process. The influence of (i) the concentration of the dispersion stabilizer and (ii) the alumina content upon the shape, size, and size distribution of the acrylic beads was studied. Cements were prepared from each batch by hand-mixing alumina-filled acrylic beads with a liquid monomer mixture containing methyl methacrylate, n-butyl methacrylate, and N,N-dimethyl-p-toluidine. Benzoyl peroxide was previously added to the solid part. The powder-to-liquid ratio was equal to 2 for each formulation. Compressive strength of cured cement decreases with alumina content, whereas compressive modulus remains roughly constant. These results are in contradiction to those obtained for cements based on a mixture of gamma-MPS-treated alumina and unfilled acrylic beads. Nevertheless, they are interpreted in terms of alumina arrangement in the cement. In the first case, alumina particles contribute to the reinforcement of the dispersed acrylic phase, with poor benefits for the whole materials. In the second case, they allow the reinforcement of the continuous acrylic phase and, therefore, the cement's one.

Acrylates↗

PMMA-based composite materials with reactive ceramic fillers: part III: radiopacifying particle-reinforced bone cements.

New acrylic bone cements were prepared from alumina particles previously treated by 3-(trimethoxysilyl)propylmethacrylate (gamma-MPS), able to act both as radiopacifying and reinforcing agents. The present study deals with the handling characteristics and the compressive behavior of such cements. The influence of the particles morphology, their surface-modification by gamma-MPS bonding agent, their concentration in the cement, the powder-to-liquid ratio and the benzoyl peroxide concentration are reported. The role of grafted gamma-MPS molecules as coupling agent was confirmed. For several formulations, compressive strength and modulus reached 150 MPa and 3400 MPa respectively. Limitations in the use of such formulations are also comprehensively discussed.

Journal Article↗

Brain endogenous insulin effects on neurite growth within fetal rat neuron cell cultures.

We have previously described insulin to be synthesized "de novo" within the fetal rat brain and that brain endogenous insulin [I(n)] promoted neurofilament distribution within fetal neurons. In this study, we investigated the role of I(n) in neuron axonal growth. Rat fetal brain stem cells from 16-day gestational age were cultured in an IFDM and treated with an insulin antibody. In addition, the cell cultures were also treated in defined medium with the addition of: 5 ng, 20 ng or 100 ng/ml of insulin or 100 ng/ml insulin-like growth factor 1 (IGF-1). The neuron cell cultures were studied at 1 and 3 days of incubation. The presence of preproinsulin mRNA and insulin immunoreaction confirmed the "de novo" synthesis of insulin by the fetal neuron cell cultures. Axonal growth was similar by day 1 of the study in all the media, but in insulin medium containing 100 ng/ml of insulin the axonal length was significantly longer. By day 3 of incubation I(n) promoted axonal growth. Treating the neurons with an insulin antibody confirmed these findings, with a significant decrease in axonal length (p<0.05). The treatment with different concentrations of exogenous insulin did not promote axonal growth beyond I(n) by day 3 of incubation. IGF-1 did not promote axonal growth by day 3 of incubation. In summary, I(n) may promote axonal growth during brain development.

Animals↗

Effects of brain endogenous insulin on neurofilament and MAPK in fetal rat neuron cell cultures.

We demonstrated the 'de novo' synthesis of insulin within the fetal nervous system in vivo and in vitro. We undertook this study to show a role for brain endogenous insulin within the fetal brain. We used neuron cell cultures (NCC) from 19 days gestational age fetal rat brains incubated in an insulin free/serum free defined medium. The neurons showed the presence of preproinsulin I and II mRNA using polymerase chain reaction and insulin immunoreaction employing peroxidase anti-peroxidase and radioimmunoassay techniques. Using an anti-pan neurofilament antibody (that recognizes non-phosphorylated neurofilaments) neurofilament immunoreaction (NFI) was observed within the neuron body, dendrites and axon. Either insulin antibody or isoproterenol treatment induced the neurites to retract and most of the neurons become round, with NFI confined to the neuron body. The antibody treatments induced the neurons to become hypertrophic and vacuolated. With PD98059 treatment NFI was only observed within the neuron body. The addition of insulin reversed the effects of isoproterenol and PD98059, but not those of the insulin antibody. Treatment with wortmannin had no effect. Western blot analysis showed that the basal level of mitogen activated protein kinase (MAPK) phosphorylation was inhibited by the treatment of the NCC with isoproterenol or trypsin, but was significantly increased by treatment with exogenous insulin, demonstrating that brain endogenous insulin phosphorylated MAPK (p<0.05). Thus, brain endogenous insulin promotes neurite outgrowth, probably via MAPK and by stimulating neurofilament distribution via this mechanism participates in neuron differentiation.

Animals↗

Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography.

BACKGROUND: Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke. METHODS: To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups. RESULTS: A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years) were enrolled; 63 were randomly assigned to receive transfusions and 67 to receive standard care. At base line, the transfusion group had a slightly lower mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the transfusion group, and two patients crossed over from the standard-care group to the transfusion group. There were 10 cerebral infarctions and 1 intracerebral hematoma in the standard-care group, as compared with 1 infarction in the transfusion group -- a 92 percent difference in the risk of stroke (P<0.001). This result led to the early termination of the trial. CONCLUSIONS: Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography.

Adolescent↗

Stroke prevention trial in sickle cell anemia.

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Adolescent↗

Successful treatment of relapsed infant acute lymphoblastic leukemia with intensive antimetabolite-based chemotherapy.

PURPOSE: The treatment of infant acute lymphoblastic leukemia (ALL) continues to be a significant challenge for pediatric oncologists due to the high incidence of early relapses. Salvage regimens used to date have met limited success. We describe two cases of relapsed infant ALL who have achieved long-term survival with an intensive antimetabolite-based salvage regimen. PATIENTS AND METHODS: Two consecutive infants with relapsed ALL presented at our institution and were treated with an antimetabolite-based regimen. Both cases exhibited clinical and biological phenotypes previously associated with infantile ALL. RESULTS: Both patients have achieved prolonged and sustained remissions 48 and 30 months EFS respectively following therapy with intensive antimetabolite-based salvage regimen. CONCLUSIONS: An intensive multiagent antimetabolite based salvage regimen resulted in prolonged EFS in two cases of relapsed infant ALL. Dose intensification was achieved by administering repeated cycles of the same treatment schema using high dose chemotherapy throughout therapy. These infants were spared prophylactic cranial irradiation without a negative impact on outcome. The use of L-asparaginase, timed after high-dose Cytarabine (ARA-C) throughout therapy, might have contributed to their cure.

Antimetabolites, Antineoplastic↗

A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group.

BACKGROUND: Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose. METHODS: We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2). RESULTS: Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome. CONCLUSIONS: A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications.

Adolescent↗

Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.

OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke.

Adolescent↗

Incidence of calcifications in the breast after surgical reduction and liposuction.

Liposuction of the breast in combination with vertical mammaplasty was applied to 250 breasts among 386 reductions of large breasts performed in 2 years (1989 to 1991). To evaluate the possible damage to the breast caused by this combined procedure, especially in terms of the occurrence of the postoperative development of calcifications, a comparative study of preoperative and postoperative mammograms was undertaken in 60 randomly selected cases (120 breasts), 34 with and 26 without liposuction. Altogether, 13 calcifications (11 percent) were discovered during the 6- to 30-month follow-up, representing the lowest rate reported in the literature. Deep intraparenchymal calcifications were more frequent after liposuction; most (5 of 7) were macrocalcifications. None could be confused with malignant calcifications because they were more scattered, more regular, and less numerous. Attempts to evaluate the fat content of breasts via preoperative mammography failed to prove this examination a useful way to predict the viability of breast liposuction.

Adult↗

Hemolytic jaundice due to G6PD deficiency causing kernicterus in a female newborn.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited deficiency of an enzyme necessary to protect the erythrocyte from oxidative stress and hemolysis. Without this enzyme, affected neonates are at risk for acute onset of hemolytic jaundice and severe sequelae, from hearing loss and mild retardation to kernicterus. In some populations, especially in blacks and those of Mediterranean ancestry, the incidence of G6PD deficiency has been reported to be as high as 10% to 14%. We describe a female newborn who had acute onset of hyperbilirubinemia leading to kernicterus in the first week of life. Investigation proved G6PD deficiency. This case suggests a need to screen for this disease or to follow serial bilirubin levels in populations at risk.

Anemia, Hemolytic↗

Effects of CD34+ selection and T cell immunodepletion on cord blood hematopoietic progenitors: relevance to stem cell transplantation.

Cord blood (CB) has been used recently for stem cell transplantation. We have investigated two different approaches to deplete CB samples of T cells capable of mounting graft-vs.-host disease (GVHD). The methods used were selection of CD34+ cells using avidin-biotin columns (CellPro) and T cell immunodepletion with T10B9 monoclonal antibody (mAb) plus complement. Using the avidin-biotin columns, 10.3% of the original CD34+ cells were recovered. Although this technique yielded a population containing 60 +/- 5.5% CD34+ cells, about 1 log of CFU-GM progenitors were lost. In contrast, after the T10B9 mAb and complement immunodepletion, 75 +/- 19% and 62 +/- 7% of the CD34+ cells and CFU-GM were recovered, respectively. T cell depletion was 3.6 logs using the CellPro columns and 2.2 logs after immunodepletion. To investigate whether cell losses following T cell depletion could be overcome by ex vivo expansion, cells were cultured in the presence of recombinant human interleukin-3 (rhIL-3) and recombinant human c-kit ligand (stem cell factor [rhSCF]) for 7 days. There were 14- and six-fold expansions in the number of progenitors recovered after CellPro and immunodepletion, respectively. To asses the engraftment potential of expanded cells, we used a murine transplantation model in which the presence of human cells was identified by the anti-CD45 mAb. Cells expanded in vitro engrafted in irradiated BNXid mice as efficiently as nonexpanded cells, suggesting that expansion did not affect their transplantability. This study shows that both techniques resulted in significant T cell depletion of CB. Furthermore, in vitro expansion could overcome cell losses sustained during the separation techniques without impairing the engraftment potential of the expanded cells.

Animals↗