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Biomedical subjects

H Mahmoud

Publications and source records attributed to H Mahmoud.

At least 19 recordsLinked to original sources

Chemistry of styrene (water)n clusters, n = 1-5: spectroscopy and structure of the neutral clusters, deprotonation of styrene dimer cation, and implication to the inhibition of cationic polymerization.

The styrene-water binary clusters SW(n), with n = 1-5 have been studied by the (one-color) resonant two-photon ionization technique using the resonance of styrene. The structures and energetics of the neutral clusters are investigated using a search technique that employs Monte Carlo procedure. The strong tendency for water molecules to form cyclic hydrogen-bonded structures is clearly observed in the SW(n) structures starting from n =3. The results indicate that the spectral shifts correlate with the interaction energies between styrene and the water subcluster (W(n)) within the SW(n) clusters. Evidence is presented that points to (1) the formation of a covalent bonded styrene radical cation dimer following the 193 nm MPI of styrene neutral clusters, (2) proton transfer from the styrene dimer cation to the water or methanol subcluster, resulting in the formation of protonated water or methanol clusters and a styrene dimer radical, and (3) extensive solvation of the styrene dimer radical within the protonated solvent molecules. The proton-transfer reactions may explain the strong inhibition effects exerted by small concentrations of water or methanol on the cationic polymerization of styrene. These results provide a molecular level view of the inhibition mechanism exerted by protic solvents on the cationic polymerization of styrene.

Journal Article↗

Maternal health in the eastern Mediterranean region of the World Health Organization.

Globally, progress in improving the survival and well-being of mothers has been slow, and this holds true for the Eastern Mediterranean Region. Thus at the current pace, it is unlikely that the Millennium Development Goal related improving maternal health will be achieved in the Region by the year 2015. This paper outlines the factors contributing to maternal mortality and poor health in the Region and the challenges faced. The action needed to redress the situation and improve maternal health, and hence achieve the fourth Millennium Development Goal, is presented.

Developing Countries↗

Reducing maternal mortality in the eastern Mediterranean region.

Current efforts in some countries of the Eastern Mediterranean Region are still insufficient to achieve the fifth Millennium Development Goal on improving maternal health. Strong commitment, intensive efforts and effective national policies and strategies are now urgently required in order to translate vision into action. Such efforts and plans should target the strengthening of health systems, the expansion in the coverage of effective integrated interventions, and the recognition of the essential role of individuals, families and communities in making pregnancy safer. This article provides a background on the current situation of maternal health in the Eastern Mediterranean Region, including underlying causes and contributing factors, and describes strategic directions aimed at accelerating the reduction of maternal mortality in the Region and moving closer to the achievement of the Millennium Development Goals.

Causality↗

Possible new role for angiotensin-converting enzyme inhibitors in treating glomerulonephritis.

Serum transforming growth factor-beta (TGF-beta1) production was estimated for 10 patients with essential hypertension, 12 patients with glomerulonephritis (5 hypertensive and 7 normotensive) and 10 healthy controls. The glomerulonephritis group received angiotensin-converting enzyme inhibitor captopril 25-75 mg/day for 4 weeks. Blood urea, serum creatinine, 24-hour urinary protein and serum TGF-beta1 were then re-estimated. Urea and creatinine were significantly higher in the hypertension and glomerulonephritis groups than in the controls and also higher in the glomerulonephritis group than the hypertension group. TGF-beta1 was significantly higher in the glomerulonephritis groups than in the control and hypertension groups. TGF-beta1 and 24-hour urinary protein were significantly reduced in the glomerulonephritis group.

Adult↗

Intensive chemotherapy with hematopoietic stem-cell support for children with recurrent or refractory NHL.

BACKGROUND: Children with refractory or recurrent NHL are generally thought to have a poor prognosis. Those with chemosensitive disease are usually considered for an intensification phase, with either autologous or allogeneic hematopoietic stem-cell transplantation (HSCT). METHODS: From 1990 to 2001 we performed 24 HSCTs in 22 children with refractory (n = 8), recurrent (n = 13), or high-risk in first CR (n = 1) NHL. Among the HSCTs, 19 were autologous and five were allogeneic. RESULTS: In two children, allogeneic HSCT was performed after failing autologous HSCT. The histologic subtypes comprised large cell, (n = 13), Burkitt's lymphoma (n = 5) and lymphoblastic (n = 4). Among the cases of primary relapse, 10 occurred during therapy and three occurred after completing initial therapy. Among the 22 children in this series, two died of transplant-related toxicity and nine died of progressive disease or relapse after transplant. Among the 11 children who are alive and disease-free, 10 had non-lymphoblastic histology and one had lymphoblastic disease; one relapsed after autologous HSCT, but was successfully salvaged with multi-agent chemotherapy and involved-field irradiation. Among the 22 initial transplanted cases, 10 of 19 children with chemosensitive disease before transplantation and one of three with chemoresistant disease are currently alive and disease-free. DISCUSSION: Intensive chemotherapy followed by hematopoietic stem-cell support is an effective strategy for children with chemosensitive recurrent non-lymphoblastic NHL.

Adolescent↗

Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases.

PURPOSE: To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML). PATIENTS AND METHODS: Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m(2)/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy. RESULTS: Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P =.002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA. CONCLUSION: This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.

Adolescent↗

Outcome after repair of tetralogy of Fallot in the first year of life.

BACKGROUND: The purpose of this study was to evaluate the early and late outcome after repair of tetralogy of Fallot in the first year of life. METHODS: Between 1974 and 2000, 89 consecutive infants with a mean age of 6.3 +/- 2.6 months (range, 15 days to 12 months) underwent repair of tetralogy of Fallot (ventricular septal defect and pulmonary stenosis) by one surgeon (J.L.M.). Three infants had previous palliative operations. Sixty-seven procedures were urgent or emergency. A transannular patch was inserted in 69 patients (77.5%). Follow-up was complete, averaging 13.4 +/- 5.6 years (range, 0 to 25.4 years). RESULTS: There was one operative death (1.1%). Mean right ventricular to left ventricular pressure ratio postoperatively was 0.4 +/- 1.1 (in 79 patients, < 0.5). Fourteen patients underwent reoperations or reinterventions. There were no reoperations for residual or recurrent ventricular septal defect. Kaplan-Meier freedom from reoperation or reintervention for any cause at 20 years was 85% +/- 4.4%, for relief of right ventricular outflow tract obstruction it was 94% +/- 3.1%, and for pulmonary valve replacement this was 95.4% +/- 2.6%. Use of a transannular patch did not significantly affect the need for reoperation or reintervention. There was one late death (leukemia). Kaplan-Meier 20-year survival was 97.8% +/- 1.9%. On latest echocardiography, 42 patients had moderate pulmonary regurgitation, 4 had a right ventricular outflow tract gradient more than 40 mm Hg, and 86 had good biventricular function. Twelve-lead electrocardiography was performed in all and 24-hour electrocardiography in 61 patients. One patient (1.1%) exhibited late recurrent ventricular tachycardia requiring implantation of a defibrillator. The remaining 86 patients are in New York Heart Association class I with none of them receiving antiarrhythmic medications. CONCLUSIONS: These data strongly support the concept of early repair of tetralogy of Fallot. It is associated with an acceptable operative risk and a low incidence of significant arrhythmias, and provides long-term survival similar to that observed in the general population. Late complications may, however, develop, and long-term follow-up for their early recognition is essential.

Adolescent↗

Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non Hodgkin's lymphoma: a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) adopted a histology-based approach to the management of pediatric non-Hodgkin's lymphomas (NHL) utilizing the National Cancer Institute Working Formulation for Clinical Usage. Patients with diffuse large cell lymphoma (DLCL) were treated on a separate protocol from small cell diffuse undifferentiated or lymphoblastic lymphomas. This study assessed the overall and event free survival of children with DLCL and determined the effects of cyclophosphamide upon these end-points in a prospective randomized trial. One hundred and twenty eligible stage III or IV NHL patients with the confirmed diagnosis of diffuse large cell or immunoblastic histology were enrolled on study between October 1986 and November 1991. Patients were randomized to receive or not receive cyclophosphamide; 58 received cyclophosphamide, doxorubicin, vincristine, 6-mercaptopurine (6-MP), and prednisone (ACOP+) and 62 were treated with doxorubicin, vincristine, 6-MP, and prednisone (APO). In both treatment programs methotrexate was substituted when the doxorubicin cumulative dose reached 450 mg/m2. Radiation was administered to bulky disease if progression or no response were observed after induction therapy. Planned duration of therapy was 12 months. The 5-year event free survival (EFS) rates of patients treated with ACOP+ versus APO were 62% +/- 7% and 72% +/- 6%, respectively. While there was no statistically significant difference between the two treatment arms (p = 0.28), we can only say that we are 95% confident that the difference in 5-year EFS falls in the wide range from 28% in favor of APO to 8% favoring ACOP+. Marrow suppression was the main toxicity with one fatal infection. There were three other deaths on study due to respiratory failure in patients with mediastinal masses. Only one patient experienced cardiotoxicity requiring discontinuation of doxorubicin. Ten patients received radiation therapy to achieve. In conclusion the efficacy of elimination of cyclophosphamide from the treatment program of children and adolescents with advanced stage diffuse large cell lymphoma was inconclusive as to its effect on EFS. Furthermore, the majority of the patients (92%) did not require any radiation therapy to bulky disease indicating that the chemotherapy regimens are quite efficient for achievement of complete remission.

Adolescent↗

Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia.

Although high-dose methotrexate has been extensively studied in children with newly diagnosed acute lymphoblastic leukemia (ALL), there are fewer data in children with relapsed ALL, many of whom have been heavily pretreated and have subclinical kidney dysfunction. We characterized the pharmacokinetics of adaptively controlled methotrexate given as a 24-h infusion during consolidation therapy in 24 children with relapsed ALL. To achieve the target steady-state concentration of 65 microM, dosage adjustments were required in 14 patients, with doses ranging from 2854 to 6700 mg/m2 per course. The mean steady-state plasma concentration (Cpss) of 68.0 microM was different (P = 0.025) than the predicted Cpss (mean = 87.4 microM; range 35.7-184 microM) had no adjustment in dose been made. The coefficient of variation in Cpss was reduced from 41% to 18% by individualizing doses. Predisposing factors that correlated with decreased methotrexate clearance were female sex (P = 0.03), age greater than 6 years (P = 0.01), and prior history of heavy amphotericin B treatment (>30 mg/kg) (P = 0.03), but no factor predicted low clearance as well as the measured initial methotrexate clearance during the infusion (P < 0.0001). There was no life-threatening toxicity with the regimen. We conclude that dosage individualization decreases interpatient variability and avoids potentially toxic methotrexate exposures in heavily pretreated ALL patients.

Adolescent↗

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation.

In this randomized prospective study, we included 30 patients with different hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the median nucleated cell count harvested was 1.3 x 10(10), while in the PBSC group, the aphereses contained a median of 4.4 x 10(6) CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 x 10(9)/l (log-rank P value <0.0018) and platelet count >25 x 10(9)/l (log-rank P value <0.0098). Seven patients (46.7%) in the BM group vs only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that seen with BMT.

Adult↗

Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation.

PURPOSE: To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23,p13.3) translocation. PATIENTS AND METHODS: A retrospective analysis of leukemic cell karyotypes obtained from patients with new diagnoses of ALL who were treated at St. Jude Children's Research Hospital or by the Pediatric Oncology Group was performed to identify cases with the t(11;19)(q23;p13.3) translocation. Molecular analyses were performed on these cases to determine the status of the MLL gene and the presence of the MLL-ENL fusion transcript. RESULTS: Among 3,578 patients with ALL and successful cytogenetic analysis, we identified 35 patients with the t(11;19)(q23;p13.3) translocation: 13 infants and 11 older children had B-precursor leukemia, whereas 11 patients had a T-cell phenotype. Although all of the cases examined had MLL rearrangements and MLL-ENL fusion transcripts, outcome varied according to age and immunophenotype. Among B-precursor cases, only two of the 13 infants remain in complete remission, compared with six of the 11 older children. Most strikingly, no relapses have occurred among B-precursor patients 1 to 9 years of age or among T-cell patients. CONCLUSION: Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis. Our results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.

Adolescent↗

Randomized trial of r-metHu granulocyte colony-stimulating factor in an intensive treatment for T-cell leukemia and advanced-stage lymphoblastic lymphoma of childhood: a Pediatric Oncology Group pilot study.

PURPOSE: Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL). PATIENTS AND METHODS: This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C). RESULTS: Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy. CONCLUSION: r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.

Adolescent↗

[Causal assessment of drug-induced acute colitis. A prospective study of 58 consecutive cases].

AIMS: The causal effect of drugs is underestimated in patients with inflammatory bowel disease. The aim of this study was to assess the causal implication of drugs in acute colitis. METHODS: A prospective study was conducted in 58 consecutive patients with an acute inflammation of the colonic mucosa. Recent drug intake was recorded and possible causal effects were analyzed exhaustively with respect to both intrinsic and bibliographic criteria. RESULTS: Causal assessment scores were high for 57 drugs and 41 patients. Drug-induced acute colitis was diagnosed in 35 cases. In 7 patients, physician practice had not taken into account drug use despite probable drug involvement. The main drugs implicated were antibiotics (n = 42) and non steroidal anti-inflammatory drugs (n = 10). CONCLUSION: Acute colitis is mainly induced by drugs.

Acute Disease↗

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

Analysis of Variance↗

Comparative cytotoxicity of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia.

PURPOSE: The relative cytotoxicity of prednisolone and dexamethasone in acute lymphoblastic leukemia (ALL) is controversial. We therefore compared the direct antileukemic activities of these compounds in stroma-supported cultures of leukemic lymphoblasts. MATERIALS AND METHODS: Bone marrow samples from children with B-lineage ALL were cultured on allogeneic bone marrow-derived stromal layers and exposed to various concentrations of glucocorticoids. After 4 days of culture, the number of viable leukemic cells was counted by flow cytometry and compared with that in parallel cultures without drugs. RESULTS: In 28 B-lineage ALL samples tested, the concentration producing 50% cytotoxicity (LC50) of prednisolone ranged from 2.0 to 7,978 nmol/L (median, 43.5 nmol/L), and that of dexamethasone from 0.6 to 327 nmol/L (median, 7.5 nmol/L). Despite the wide variability of responses among samples, there was an excellent correlation between LC50 values obtained with the two drugs (linear r = .99, P < .0001; Spearman rank-order r = .77, P < .0001). The median ratio of dexamethasone to prednisolone LC50 and LC90 values was 1:5.5 (range, 1:1.0 to 1:24.4 for LC50; 1:1.1 to 1:25.5 for LC90). Studies with ALL cell lines demonstrated that both drugs were cytotoxic through induction of apoptosis. Stromal layers did not absorb or inactivate measurable amounts of corticosteroids, which indicates that the assay system did not bias results toward increased drug resistance. CONCLUSION: In a bone marrow-derived microenvironment, dexamethasone is five to six times more cytotoxic (on a molar basis) than prednisolone, in agreement with the antiinflammatory activities of these drugs. This finding may serve to guide the selection of dexamethasone dosage in the treatment of ALL.

Adolescent↗

Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia.

Early response to therapy, typically assessed by bone marrow status, is predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is known about the significance of early clearance of blast cells in peripheral blood. We reviewed medical records of all patients with ALL enrolled on St Jude Total Therapy Study XI (February 1984 to September 1988) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. Of the 358 patients, 59 lacked evidence of circulating blast cells at diagnosis, and data were unavailable for 2 patients. The prognostic significance of persistent circulating blast cells in the remaining 297 patients was assessed in a multivariate analysis that included known adverse prognostic factors. Persistent circulating leukemic blasts were present at day 8 in 41 patients (14%). Compared with the "blast-negative" group, these patients had a significantly higher frequency of several adverse clinical features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology) and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/- 3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the most significant adverse feature in the overall cohort (relative risk, 2.9; 95% confidence interval, 1.8 to 4.8) and in an analysis limited to B-lineage cases (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by this simple, noninvasive measure may benefit from early modification of therapy.

Antineoplastic Combined Chemotherapy Protocols↗