Search PubMed⌕ Search

Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 55 records · Page 3Linked to original sources
PubMed1999

Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol.

BACKGROUND: Severely malnourished children have high mortality rates. Death commonly occurs during the first 48 h after hospital admission, and has been attributed to faulty case-management. We developed a standardised protocol for acute-phase treatment of children with severe malnutrition and diarrhoea, with the aim of reducing mortality. METHODS: We compared severely malnourished children with diarrhoea aged 0-5 years managed by non-protocol conventional treatment, and those treated by our standardised protocol that included slow rehydration with an emphasis on oral rehydration. The standardised-protocol group included children admitted to the ICDDR,B Hospital, Dhaka between Jan 1, 1997, and June 30, 1997, while those admitted between Jan 1, 1996, and June 30, 1996, before the protocol was implemented, were the non-protocol group. FINDINGS: Characteristics on admission of children on standardised protocol (n=334) and non-protocol children (n=293) were similar except that more children on standardised protocol had oedema, acidosis, and Vibrio cholerae isolated from stools. 199 (59.9%) of children on standardised protocol were successfully rehydrated with oral rehydration solution, compared with 85 (29%) in the non-protocol group (p<0.0001). Use of expensive antibiotics was less frequent in children on standardised protocol than in the other group (p<0.0001). Children on standardised protocol had fewer episodes of hypoglycaemia than non-protocol children (15 vs 30, p=0.005). 49 (17%) of children on non-protocol treatment died, compared with 30 (9%) children on standardised protocol (odds ratio for mortality, 0.49, 95% CI 0.3-0.8, p=0.003). INTERPRETATION: Compared with non-protocol management, our standardised protocol resulted in fewer episodes of hypoglycaemia, less need for intravenous fluids, and a 47% reduction in mortality. This standardised protocol should be considered in all children with diarrhoea and severe malnutrition.

Anti-Bacterial Agents↗
PubMed1999

Neuroleukin mediated differentiation induction of myelogenous leukemia cells.

Leukemia cells enriched from peripheral blood of a patient with myelogenous leukemia were induced to differentiate with a purified T cell lymphokine neuroleukin. With sufficient neuroleukin concentrations, cells with macrophage-like morphology were identified among the developing adherent cells. After 2-5 days, approximately 38-50% of the suspension cells became macrophage-like and acquired CD21, alpha-naphthyl acetate reactivity and immune adherence capability. The amount of these nonproliferating cells increased along with cells containing fragmented DNA. Induction with insufficient neuroleukin quantity or with patient plasma alone developed few or no mature cells, indicating differentiation to mature cells is dose-dependent. The possibility of insufficient quantity of neuroleukin in regulation of patient plasma for differentiation was discussed.

Cell Differentiation↗
PubMed1999

Human CD34+ hematopoietic cells transduced by retrovirus-mediated interferon alpha gene maintains regeneration capacity and engraftment in NOD/SCID mice.

To achieve long-term expression of human interferon alpha-5 (IFNalpha) gene in the bone marrow (BM) hematopoietic microenvironment, replication-deficient retroviral vector LSN-IFNalpha was used to deliver the IFNalpha gene into human BM CD34+ cells. After fibronectin-facilitated transduction, a fraction of CD34+ cells was plated in methylcellulose medium with or without G418 to assess transduction efficiency and the effect of IFNalpha gene transfer on colony formation. Colony-forming assay in the presence of G418 (400 microg/mL) revealed that 41% CFU-GM colonies are G418 resistant after infection with LSN-IFNalpha retrovirus. There was no significant difference in CFU-GM/BFU-E colony formation among IFNalpha gene-transduced CD34+ cells, control vector (LXSN) transduced-CD34+ cells and nontransduced CD34+ cells. Another portion of CD34+ cells was grown in liquid medium to measure IFNalpha production. RIA revealed that IFNalpha gene-transduced CD34+ cells produced 72.2 +/- 15.4 U/mL (10(6) cells/24 hours) of IFNalpha compared with 8.3 +/- 2.1 U/mL and 4.3 +/- 1.2 U/mL in LXSN-transduced or nontransduced CD34+ cells, respectively. The remaining portion of transduced CD34+ cells was transplanted into immunodeficient (NOD/SCID) mice to allow analysis of long-term expression of IFNalpha. Transplantation of 1x10(6) CD34+ cells into sublethally irradiated NOD/SCID mice showed that IFNalpha and neo(r) mRNA were detectable in engrafted mouse BM cells for up to 6 months. We conclude that continual local expression of IFNalpha in transduced CD34+ cells does not impair either CD34+ cell growth and differentiation or engraftment and long-term survival in NOD/SCID mice.

Animals↗
PubMed1999

Phase II clinical trial of didemnin B in patients with recurrent or refractory anaplastic astrocytoma or glioblastoma multiforme (NSC 325319).

The activity of didemnin B, a natural product derived from the Caribbean Tunic was assessed in 16 patients with Glioblastoma multiforme. Didemnin B was administered intravenously by a short infusion at a dose of 4.3 mg/m2 and subsequently escalated to 6.3 mg/m2. No anti-tumor activity was observed. Toxicity consisted of fatigue, weakness, stomatitis, mild blood count changes, nausea and vomiting and occasional fever. Based on these results further studies with didemnin B in patients with Glioblastoma multiforme are not recommended.

Adult↗
PubMed1999

Cyclosporine-induced autologous graft-versus-host disease in patients with acute myeloid leukemia undergoing non-myeloablative chemotherapy without progenitor cell reinfusion.

To determine the incidence and severity of cyclosporine-induced graft-versus-host disease following non-myeloablative chemotherapy without progenitor cell reinfusion in patients with acute leukemia, 17 adults with refractory acute myeloid leukemia (14) or blastic phase of chronic myeloid leukemia (3) were treated with etoposide 2400 mg/m2 and cyclophosphamide 120 mg/kg followed by cyclosporine (CsA) 2.5 mg/kg i.v. daily and interferon gamma 0.025 mg/m2 subcutaneously every other day until day 28. Skin biopsies were obtained on days 14 and 28, or on the appearance of a skin rash, and graded for GVHD. Blood samples were examined at baseline and weekly starting on day 14 for natural killer (NK) cell and T cell lymphocytic changes. Post-treatment lymphocytes from select patients were assessed for allogeneic NK cell and autologous leukemic cell cytolytic activity. Four patients developed pathologic grade 2 cutaneous acute GVHD. Of the three patients who achieved a complete remission, two had evidence of GVHD. Post-treatment, three patients (two with GVHD) in whom adequate numbers of lymphocytes could be obtained showed NK cell cytolytic activity against allogeneic tumor cells (K562), but none had cytolytic activity against their own cryopreserved leukemic cells. These data suggest that in patients with AML treated with subablative doses of chemotherapy without autotransplant, autologous GVHD can be induced, although at an incidence lower than that reported for CsA-induced GVHD following marrow transplantation. An enhancement of T cell and NK cell activity levels similar to experiences in syngeneic models of autologous GVHD was seen, but no direct autologous leukemic cell cytotoxicity could be demonstrated.

Adult↗
PubMed1999

Activation of the acidic isoform of phospholipase A2 from Naja mossambica mossambica venom by oleoyl imidazolide requires the cooperative action of two ionizing groups.

The acidic phospholipase A2 isoform from the spitting cobra Naja mossambica mossambica is activated irreversibly by treatment with a molar equivalent of oleoyl imidazolide. The kinetics of the chemical modification of the enzyme can also be monitored by measuring the large reduction of tryptophan fluorescence, which is accompanied by a distinct red shift. The addition of a single molar equivalent of oleic acid to the enzyme produces an instantaneous reduction in fluorescence but with a barely detectable red shift, confirming that the response to oleoyl imidazolide results from covalent modification of the protein rather than hydrolysis of the reagent. The pH dependence of both activation and fluorescence reduction by oleoyl imidazolide has an optimum rate near pH 8.0. We propose that long-chain fatty acids and long-chain acyl imidazolides bind at a single activation site and that the reaction of the imidazolides involves two protein residues, one of which is a nonessential histidine residue and the other a primary amino group.

Animals↗
PubMed1999

Distinct effect of retroviral-mediated IFN-alpha gene transfer on human erythroleukemic and CD34+ cell growth and differentiation.

Human interferon-alpha (IFN-alpha) has been used in the management of leukemia, but its diverse adverse effects may influence the ability of IFN-alpha to treat this disease. We constructed two retroviral vectors, LSN-IFN-alpha and LNC-IFN-alpha, in which IFN-alpha cDNA was driven by viral LTR and CMV promoters, respectively. After transduction into the PA317 and PG13 retroviral packaging cells, high titers of retrovirus were produced and were used to infect K562 and human BM CD34+ hematopoietic cells. The IFN-alpha gene expression in transduced K562 cells was confirmed by Northern blot, RT-PCR, RIA, and biologic assay. Cell proliferation and cell viability in IFN-alpha-transduced K562 cells were significantly suppressed as compared with control K562 cells. Although the IFN-alpha expression in K562 cells did not affect BCR/ABL expression, it apparently upregulated the production of adhesion molecules (VLA-4 and Mac-1). We evaluated the effect of IFN-alpha gene transfer on human CD34+ cells infected with LSN-IFN-alpha retrovirus with the aid of fibronectin (FN) fragment CH-296 and growth factors. RIA showed that IFN-alpha-transduced CD34+ cells produced 72.2+/-15 U/ml of IFN-alpha compared with 4.3+/-1.2 U/ml in control CD34+ cells. Methylcellulose clonogenic assay indicated that IFN-alpha-transduced CD34+ cells produced similar numbers of burst-forming units-erythrocytes (BFU-E)/colony-forming units-GM (CFU-GM) colonies as compared with control CD34+ cells. Selected colonies expressed IFN-alpha and neo(r) mRNA, as measured by RT-PCR. These studies indicate that retrovirus-mediated IFN-alpha gene transfer may provide a useful tool for studying the effect of IFN-alpha gene transfer on leukemic cells and long-lived CD34+ cells.

Antigens, CD↗
PubMed1999

Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses.

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by "nonanticoagulant fractions" (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n = 8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg), whereas ULMW NAF-heparin (n = 7) was the most effective agent (ABR ID50 = 0.4 mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered "after" antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.

Animals↗
PubMed1999

Effect of an educational multimedia prostate program on the International Prostate Symptom Score.

OBJECTIVE: To determine the effect of an interactive multimedia prostate education program (MMP) on self assessment of symptom scores due to benign prostatic hyperplasia (BPH). METHODS: The interactive MMP was developed including a computer-administered version of the International Prostate Symptom Score (IPSS) questionnaire. Eighty-eight men referred to the Urology Out-patients with prostatic symptoms entered the study. They first completed the IPSS on paper and secondly used the MMP before completing the computer-administered IPSS. A final feedback questionnaire enquiring into their experience including previous exposure to computers, ease of use, and value of the program content was completed. RESULTS: The use of the MMP resulted in a significant decrease in mean IPSS score from 16.6 to 13.9 (t = 7.456, d.f. = 87, p < 0.01), but no change in quality of life. Patients felt that their knowledge had increased (chi2(1) = 21.253, p < 0.01) and that they had completed the IPSS more accurately (chi2(1) = 10.227, p < 0.01) with the MMP IPSS module compared to the IPSS on paper. Previous use of patient education, patient characteristics and MMP use beyond the information required for the IPSS did not affect IPSS difference (IPSS before versus after MMP use). CONCLUSION: The use of the MMP enhanced patients' knowledge of their condition and reduced patients' IPSS score. The results were independent of previous exposure to information, previous IPSS completion, computer use and age.

Aged↗
PubMed1999

Synergetic effects of retrovirus IFN-alpha gene transfer and 5-FU on apoptosis of colon cancer cells.

Gene transfer has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells including the most primitive stem cells and cancer cells. Several investigators have reported on the clinical effects of interferon-alpha (IFN-alpha) or the combination of 5-FU plus IFN-alpha on patients with advanced colorectal carcinoma. Therefore, we examined the ability of a retrovirus-mediated IFN-alpha gene transfer to infect colon cancer cells COLO 201 and the effect of IFN-alpha gene expression alone or in combination with other chemotherapeutic drugs as 5-FU. IFN-alpha showed positive antitumor activity against COLO 201 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against COLO 201 cells. Furthermore, we demonstrated that combination therapy of IFN-alpha gene transfer and 5-FU resulted in enhancement of cancer cell lethality. The potentiation increased with higher concentrations of 5-FU by 1.5- to 2.1-fold. Our results suggest that retrovirus-mediated IFN-alpha gene transfer in COLO 201 cells resulted in functional gene expression as assessed by the levels of IFN-alpha mRNA and protein; furthermore, the combination of IFN-alpha gene transfer and 5-FU have additional effects on the induction of apoptosis. This finding provides an experimental basis for possible clinical therapy using retrovirus-mediated IFN-alpha gene transfer alone or in combination with other chemotherapeutic drugs for treatment of colorectal cancer.

Adenocarcinoma↗
PubMed1999

Prevention of exercise-induced bronchoconstriction by inhaled low-molecular-weight heparin.

Because many biological actions of heparin including the antiallergic activity are molecular weight dependent, we hypothesized that low-molecular-weight heparin (LMWH) may have greater potency in attenuating exercise-induced bronchoconstriction (EIB). Therefore, in the present investigation we studied the effects of inhaled LMWH, enoxaparin, and unfractionated heparin on EIB in subjects with asthma. Thirteen asthmatic subjects performed a standardized exercise challenge on a treadmill to document the presence of EIB. The workload was increased until 85% of predicted maximal heart rate was achieved, and the exercise was sustained at that workload for 10 min. EIB was assessed by measuring FEV(1) before and immediately after the exercise. On five different experiment days the subjects were pretreated with 4 ml of aerosolized heparin (80,000 units = 7.5 mg/kg), placebo, or 3 different doses of enoxaparin (0.5 mg/kg, 1 mg/kg, 2 mg/kg) in a double-blind, randomized, crossover design, and exercise challenge was performed 45 min later. Bronchial provocation with methacholine was also performed in five subjects on two additional days after pretreatment with either placebo or inhaled enoxaparin (2 mg/kg), and venous blood was obtained for analysis of plasma antifactor Xa. Postexercise, the maximal decreases in FEV(1) (mean +/- SE) were 30 +/- 4% and 29 +/- 5% on control and placebo days. The exercise-induced decreases in FEV(1) were inhibited by 31% with heparin (DeltaFEV(1) = 20 +/- 4%); and by 28%, 38%, and 48% by enoxaparin at doses of 0.5 mg/kg (DeltaFEV(1) = 21 +/- 5%), 1 mg/kg (DeltaFEV(1) = 18 +/- 5%), and 2 mg/kg (DeltaFEV(1) = 15 +/- 3%), respectively (p < 0.05). The inhibitory effect of 0.5 mg/kg dose of enoxaparin was comparable to heparin (7.5 mg/kg), whereas 2 mg/ kg dose of enoxaparin was the most potent. Inhaled enoxaparin failed to modify the bronchoconstrictor response to methacholine, and did not change the plasma antifactor Xa activity. These data demonstrate that inhaled enoxaparin prevents EIB in a dose-dependent manner; and its antiasthmatic activity is independent of its effect on plasma antifactor Xa activity.

Administration, Inhalation↗
PubMed1999

Enhancement of 5-fluorouracil cytotoxicity on human colon cancer cells by retrovirus-mediated interferon-alpha gene transfer.

Gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. Several reports documented the clinical effects of interferon-alpha (IFN-alpha) in management of patients with advanced colorectal carcinoma. We report for the first time, the successful transduction of human IFN-alpha gene into colon cancer cells, COLO 201 using a replication-defective retroviral vector. Retrovirus-containing supernatant from PA 317 packaging cells was used to infect colon cancer cells, COLO 201 and NIH 3T3 cells. Transient infection showed that cell proliferation and cell viability were significantly suppressed in colon cancer cells transduced with IFN-alpha gene. Moreover, IFN-alpha-transduced cells acquired less resistance to 5-FU induced apoptosis. These data demonstrate that IFN-alpha gene transfer may have a clinical application and can be combined with chemotherapy for treatment of advanced colorectal cancer.

3T3 Cells↗
PubMed1999

Regulation of growth and apoptosis of breast cancer cells by a 54 kDa lymphokine.

A normal human lymphocyte-derived 54 kDa polypeptide, capable of regulating cell growth has been identified as an isoform variant (abbreviated as NP54) of protein neuroleukin-phosphoglucose isomerase (PGI). Since distinct PGI variants undetectable in normal tissues had been identified in breast cancer tissues, the effect of NP54 on the growth of human breast cancer cells SK-Br-3 in cultures was analyzed. Exposure to NP54 caused a dose-dependent growth modulation. Approximately 40% reduction of cell density was detected at 40 pM of NP54, along with a blocking of G1 cells entering into S phase. The growth modulation was correlated with a significantly reduced expression of epidermal growth factor receptor (EGF-R) gene transcript, supporting the interpretation that the level of EGF-R expression and cell growth are related mechanisms. NP54 treatment also significantly increased cells with apoptotic morphological feature and fragmented DNA. Incubation with a monoclonal anti-NP54 antibody negated NP54 activity, confirming a regulatory activity in cell growth and apoptosis.

Antibodies, Monoclonal↗
PubMed1999

A study of the cost effectiveness of selective health interventions for the control of intestinal parasites in rural Bangladesh.

The study examined the cost effectiveness of 4 different regimens in reducing the prevalence and intensity of infection of Ascaris lumbricoides, Trichuris trichiura, and hookworm over an 18-mo period in randomized community samples of children aged 2-8 yr living in rural Bangladesh. The household was the unit of randomization in each community. The 4 regimens were (1) only chemotherapy to all household members at the commencement of the study (i.e., at an interval of 18 mo), (2) same as group (1) and regular health education throughout the study period, (3) chemotherapy to all household members at the commencement of the study and subsequent chemotherapy to all children at intervals of 6 mo, and (4) same as group 3 with the addition of regular health education throughout the study period. Health education (through home and school visits and focus group discussions) was aimed at increasing awareness of worm transmission and the disabilities caused by intestinal helminths. Simple ways of improving personal hygiene and sanitation through hand washing, nail trimming, wearing of shoes, and use of a latrine and clean water supplies were encouraged. Because albendazole is a broad spectrum anthelmintic, the cost effectiveness of the 4 interventions were compared by the weighted percentage reduction in prevalence and the weighted percentage reduction in intensities of infection as measured by geometric mean egg loads of all 3 worms combined. The most cost-effective strategy was the single albendazole mass chemotherapy at an interval of 18 mo. The 2 regimens involving health education were the least cost effective.

Albendazole↗
PubMed1999

Adenovirus and retrovirus mediated interferon alpha gene transfer into CD34+ cells maintains regeneration capacity and enhances adhesion molecules in K562 cells.

BACKGROUND: Systemic administration of interferon-alpha (IFN-alpha) results in cytogenetic remissions and enhanced survival in a significant percentage of patients with chronic mylogenous leukemia (CML) and lymphoma. However, this treatment is associated with deleterious toxic effects. Gene transfer of the IFN-alpha gene into hematopoietic progenitors represents a novel strategy to deliver high concentrations of IFN-alpha to a local area. METHODS: We compared the effect of the transfer of the IFN-alpha gene on the cell growth and differentiation of several CD34+ cells in culture and in a NOD/SCID animal model, using adenovirus and retrovirus constructs. RESULTS: Transient local expression of the IFN-alpha gene using an adenovirus vector was associated with normal proliferation of CD34+ progenitors as measured by a colony forming unit of granulocyte-macrophage (CFU-GM) growth. Flow cytometric determination revealed that there was no significant difference in viability of these cells for 24-hour transduction periods. Reverse transcriptase/polymerase chain reaction (RT-PCR) analysis of RNA from CD34+ harvested CFU-GM progenitors demonstrated expression of IFN-alpha mRNA; radioimmunoassay (RIA) revealed that transduced cells secreted substantial levels of IFN-alpha protein. Furthermore, we constructed a retroviral vector in which IFN-alpha cDNA was driven by a viral LTR promoter to evaluate the effect of permanent IFN-alpha gene expression on cell growth. Retroviral packaging cells PA317 with high titers of retrovirus were produced and used to infect CD34+ and K562 cells. RIA showed that IFN-alpha-transduced CD34+ cells (with the aid of fibronectin fragment CH-296) produced approximately 400 units of IFN-alpha protein compared to CD34+ cells, or cells transduced with empty vector. IFN-alpha transduced CD34+ generated similar numbers of CFU-GM colonies as compared to control CD34+ cells. Engraftment of CD34+ cells transduced with IFN-alpha gene in NOD/SCID mice was successful for the first 30 days. Additionally, we studied the effect of local IFN-alpha expression on the cellular adhesion molecules, VLA-4, Mac-1, ICAM-1, and L-selectin in K562 cells, and human umbilical endothelial vein cells. K562 cells transduced with the IFN-alpha gene expressed a significantly elevated level of VLA-4, Mac-1, and ICAM-1. CONCLUSIONS: We conclude that expression of the IFN-alpha gene using retrovirus vectors results in an adequate localized expression of IFN-alpha mRNA and protein.

Adenoviridae↗