Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 19 recordsLinked to original sources

PubMed2006

Validation of the LC-MS/MS method for the quantification of mevalonic acid in human plasma and determination of the matrix effect.

A simple, specific, and sufficiently sensitive liquid chromatography-tandem mass spectrometry (negative-ion electrospray ionization) methodology to determine mevalonic acid (MVA) in human plasma is described, and its application to the analysis of rat plasma MVA levels after rosuvastatin administration is demonstrated. The method was validated over the linearity range of 0.5-50.0 ng/ml (r(2) > 0.99) using deuterated MVA as an internal standard. The lower limit of quantification was 0.5 ng/ml. The assay procedure involved the isolation of MVA from plasma samples using solid-phase extraction. Chromatographic separation was achieved on a HyPurity Advance column with a mobile phase consisting of ammonium formate buffer (10 mM, pH 8.0) and acetonitrile (70:30, v/v). Excellent precision and accuracy were observed. MVA and deuterated mevalonolactone were stable in water and plasma under different storage and processing conditions. The recovery observed was low, which was attributable to a significant matrix effect. A significant decrease (30-40%; P < 0.05) was observed in rat plasma MVA levels after rosuvastatin administration.

Animals↗

PubMed2006

Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment.

BACKGROUND: We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days. PATIENTS AND METHODS: Patients scheduled to receive cisplatin > or =70 mg/m(2) were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2-3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1-4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1-5 post-cisplatin). RESULTS: Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2-5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P < or = 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P < or = 0.001). Rates of no rescue therapy were similar between groups. CONCLUSIONS: Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC00090207.

Adult↗

PubMed2005

Extended-interval gentamicin administration in malnourished children.

Malnourished children have several physiologic abnormalities that can affect drug distribution and elimination. The aim of this study was to determine the efficacy, safety and pharmacokinetics of a once-daily dose of gentamicin compared with conventional thrice-daily dosing in malnourished children. To our knowledge, it has not been investigated in this population so far. A total of 310 malnourished children of either gender aged 6 months to 5 years with diarrhea and pneumonia were randomized to receive intramuscular gentamicin 5 mg/kg/day once-daily (OD) (n=148) or the same total daily amount given in three divided doses (TD) (n=162) in addition to ceftriaxone 75 mg/kg/day. After 48 h at steady state, gentamicin pharmacokinetics was assessed by fluorescence polarization immunoassay in a subgroup of 59 children and 43 children in the OD and TD groups, respectively. The groups were equivalent in baseline demographic, clinical and laboratory characteristics. Good and partial clinical responses occurred in 64 per cent vs. 54 per cent and 25 per cent vs. 27 per cent in the OD and the TD children, respectively (p=NS for both comparisons). Five patients in each treatment group died. Renal toxicity defined by change in serum creatinine was not observed in any patient from either group. In the OD group, mean+/-SD serum gentamicin concentrations at 1 (peak), 3, 5, 8, 23, and 24 (trough value) hours after the dose were 11.7+/-4.1, 4.4+/-1.2, 2.08+/-0.9, 1.01+/-0.6, 0.31+/-0.09 and 0.29+/-0.07 mg/l respectively. In the TD group, mean +/-SD serum gentamicin concentration at 1 hour (peak) was 4.7+/-1.8 mg/l and the trough concentration was 0.48+/-0.21 mg/l. In OD group, the gentamicin trough concentration was significantly lower (p<0.001) and the peak concentration was significantly higher (p<0.001) compared to TD group. The results of this study indicate that once-daily gentamicin is effective and safe in malnourished children. Widespread implementation of once-daily dosing in malnourished children is appropriate and will reduce number of intramuscular injections and hospital costs.

Anti-Bacterial Agents↗

PubMed2005

Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocampal slices during long-term potentiation in vitro.

Molecular events associated with mnemonic processes and neuronal plasticity are postulated to result in functional changes in synaptic structure. One possible site is the post-synaptic density, where activity-dependent changes modulate signal transduction cascades. In this report, we detail spatial-temporal changes for phosphodiesterase 4B (PDE4B) proteins and their substrate cAMP within three neuronal fractions during early and late long-term potentiation (LTP). The cAMP-dependent protein kinase A cascade--which can be regulated by distinct PDE4B activity--is required for mnemonic processes as well as mechanisms of neuronal plasticity, such as those during the maintenance or late-LTP. Fluorescence in situ hybridization studies (FISH) identified no translocation of PDE4B3 from the soma after late-LTP induction indicating a subtle, local control of PDE4B activity. Protein changes were detected within the PSD-enriched fraction. From these results, we conclude that either the changes in PDE4B are due to modulation of pre-existing mRNA, or that the protein is specifically translocated to activated synaptic structures. Furthermore, we report late changes in cAMP levels in the somato-dendritic fraction and discuss this result with the increased PDE4B1/3 doublet in the PSD-enriched fraction.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Rho family GTPases are activated during HGF-stimulated prostate cancer-cell scattering.

An important process in embryogenesis and cancer-cell metastasis is the conversion of epithelial cells to a migratory phenotype, a phenomenon known as epithelial-mesenchymal transition (E-MT). To achieve E-MT, cells dissociate from neighbouring cells and adopt a migratory morphology. This transition requires remodelling of their cell shape and substratum adhesions; activities that require extensive reorganisation of the actin cytoskeleton. Hepatocyte growth factor (HGF)-induced scattering of Madin Darby canine kidney (MDCK) cells is a routinely used model of E-MT, in which actin cytoskeletal rearrangement is known to be dependent on Rho family GTPases. We have developed a novel model of HGF-induced E-MT using the human prostate cancer cell line, DU145. This model overcomes the limitation of using a canine cell line and facilitates the study of E-MT in human cancer. We demonstrate for the first time the scattering response of individual DU145 cells to HGF in real time and have characterised changes in actin cytoskeletal organisation and cell adhesions as these cells respond to HGF. HGF-induced scattering of DU145 cells is dependent on the activity of Rho family GTPases, and using this model, we are able to demonstrate for the first time that endogenous Cdc42 is activated downstream of HGF. Furthermore we have also shown that the response of DU145 cells to HGF is dependent on a phosphatidylinositide 3-kinase pathway.

Actins↗

PubMed2005

Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant.

Dose-intensive chemotherapy with autologous stem cell support is commonly used in resistant/refractory cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the role of tandem transplantation in these patients. We used non cross-resistant conditioning regimens with thiotepa, mitoxantrone and carboplatin (TMJ) followed by ifosphamide, carboplatin and etoposide (ICE) with autologous stem cell rescue in an attempt to maximize dose intensity and achieve long-term remission. Seventy-six patients were included in this study. Twenty-nine patients with HD and 47 with NHL underwent autologous stem cell transplant using TMJ as the conditioning regimen for the first transplant. Of these, 49 patients proceeded to the second transplant using ICE as the conditioning regimen. In 57 patients, only peripheral blood cells were used and in 11 patients both bone marrow and peripheral stem cells were used. Twelve patients died due to treatment-related toxicity. On an intent to treat basis, 32.14% of patients with HD refractory to initial or subsequent therapy survived long term as opposed to 12.76% of patients with NHL. With a median follow-up of 83 months (range 25 - 110 months), the median disease-free survival of patients with HD was 7 months, as opposed to 2 months for patients with NHL. Multivariate analysis identified that patients with HD had a superior outcome if they were less than 35 years of age and did not have B symptoms. Dose-intensive chemotherapy with tandem transplantation is an option in patients with resistant/refractory lymphoma who have very limited treatment options and poor prognosis.

Adult↗

PubMed2004

The utility of a multimedia education program for prostate cancer patients: a formative evaluation.

A multimedia program (MMP) was developed to educate patients with prostate cancer about their disease. A within-subjects design was used to investigate the changes in levels of cancer-related knowledge, psychosocial functioning, treatment decision-making role and information needs immediately after browsing the MMP. The participants were 67 men recently diagnosed with prostate cancer. Psychosocial functioning was assessed with 20 items describing common emotional states and coping strategies employed by cancer patients. Treatment decision-making role was assessed with the Control Preference Scale. A principle component analysis of the 20 psychosocial items yielded three components: distress, positive approach and nonacceptance. After browsing the MMP significant increases in knowledge and reductions in distress were reported. Marital status was significantly associated with knowledge gain. Married men and those attending the study session with their spouse displayed a significant shift towards a more active role in treatment decisions. The majority of information needs were fulfilled by the MMP; however, information related to the likelihood of a cure, treatment side effects, coping strategies and aetiology were not completely satisfied by the MMP. Implications of the findings and suggestions for future work on the design and evaluation of the MMP are discussed.

Aged↗

PubMed2004

Regulation of the phosphodiesterase PDE4B3-isotype during long-term potentiation in the area dentata in vivo.

Hippocampal long-term potentiation (LTP) is the most prominent cellular model underlying learning and memory formation. However, which cellular processes are involved in maintaining LTP remains largely unknown. We have previously detailed temporal modulations of cyclic adenosine monophosphate (cAMP) and a cAMP-specific phosphodiesterase, PDE4B3, after LTP-induction and its maintenance in hippocampal area CA1 in vitro. To test whether other hippocampal sub-structures are characterised by similar mechanisms, tissue from the area dentata of freely moving rats was analysed at different LTP-time points. The tissue was fractionated into three components, where PDE4B-levels and cAMP-concentrations were measured. In contrast with data obtained in area CA1, we now detail an LTP-specific translational, but not transcriptional regulation of PDE4B3 within the first 8 h after tetanization and present spatio-temporal changes of PDE4B proteins and cAMP that is LTP-specific.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Demand-based water options for arsenic mitigation: an experience from rural Bangladesh.

A supply of safe drinking water is a recognized global concern. The arsenic contamination of groundwater in Bangladesh and other countries has furthered this concern. Lack of appropriate water options is one of the main barriers to the supply of safe drinking water for 30-60 million people who are exposed to the risk of drinking arsenic-contaminated water in Bangladesh. This paper describes the experience from a water supply programme for arsenic mitigation based on demand and participation of 30,000 rural people in Srinagar, a subdistrict of Bangladesh. About 85% of the 912 tubewell water samples tested had an arsenic content higher than 0.05 mg/l. The project promoted 11 options including groundwater, surface-water and rainwater-harvesting household-based options as well as community managed technologies. Most people, particularly women, wanted piped water, and hand-operated deep tubewells were also requested. Four cluster-based motorized piped water systems, 20 home-based arsenic-removal options (two types) and an arsenic-removal filter plant were installed. The public contributed about 49, 25 and 20% of the installation costs of piped water, home-based options and filter options, respectively, and 100% of all operation and maintenance costs. The household options and filter plant were abandoned within a few weeks. Reportedly, those options required too much attention, discharged small volumes of water at low rates, were difficult to maintain, and discharged poor-quality water. The proportion of families (54%) that drank arsenic-contaminated water during the final survey was significantly lower than in the baseline survey (87%). For arsenic-affected areas, it is recommended that a cluster-based piped water system be given proper consideration when selecting appropriate water options rather than household-based options or the development of new low-cost options.

Arsenic↗

PubMed2004

High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors.

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23-147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P=0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.

Adult↗

PubMed2004

Management of dengue by the WHO guided national guidelines.

A total of 90 adult patients of Dengue admitted in Sir Salimullah Medical College and Mitford Hospital, Dhaka during the period from July 2002 to December 2002 were studied to see the presentation, spectrum of disease and outcome of management. Majority (52%) of cases was in the age group 21-30 years. Out of 90 patients 74 patients (82.22%) were male and 16 (17.78%) were female. Maximum number of cases (43%) was found in the month of August. Most of the cases (77%) were from Dhaka City. Classical type of Dengue fever was the commonest (80%) variety. Thrombocytopenia was found in 80% cases. Platelet count came down below 10000/cumm only in 1.1% of the patients. The patients were diagnosed mainly by clinical criteria. Serological tests were done only in selected cases. Majority (80%) of the patients was managed by sponging, paracetamol and Oral Rehydration Salt (ORS). Blood transfusion was required in 18% cases and platelet concentrate was given only in 1.1% cases. There was no mortality in this study.

Acetaminophen↗

PubMed2004

Pharmacokinetic differences of some generic tablet gliclazide 80 mg on Pakistani population.

The goal of rational drug therapy is to produce a desired pharmacological response in an acceptable and predictable manner while minimizing the occurrence of undesired events. The Pharmacokinetics of different generics of tablet gliclazide 80 mg was investigated on healthy (10 x 2), Pakistani subjects. For this exploration an open-label, randomized, two-period crossover (Balanced in Complete Block Design) study, was conducted The out come of the said study suggests that all generics were found analogous regarding pharmacokinetic behavior in-spite of having different excipients, concentration of excipients, sources of raw material, manufacturing process, machinery, resources and also inter individual variation of the study. Results of the study also undoubtedly advocate that generics manufactured in different manufacturing units of Pakistan are near to the standard formulation and produce comparable results. No significant differences in pharmacokinetics parameters were observed, however, minor differences might narrate with inter individual variation in human volunteers and in different generic as well as different pharmaceutical unit.

Journal Article↗

PubMed2003

Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature.

Single-vessel cervical arterial dissections typically occur in young adults and are a common cause of cerebral ischemia and stroke. Although the pathogenesis of multivessel dissection is unclear, it is thought to be a consequence of underlying collagen vascular disease. We present a 34-year-old previously healthy man who developed bilateral internal carotid and vertebral artery dissection following chiropractic manipulation.

Adult↗

PubMed2003

The cost-effectiveness of health education in improving knowledge and awareness about intestinal parasites in rural Bangladesh.

The impact of regular health education in improving knowledge, attitude and practices in the control of intestinal parasites was examined in four rural areas of Bangladesh; two areas received health education and the other two areas were controls. By the end of the 18-month study households receiving health education showed highly significant improvements in knowledge, water and sanitation facilities and personal hygiene compared with households in the control areas. Improving knowledge by 1% cost between US dollars 0.75 and 0.82 per household, while a 1% improvement in personal hygiene cost between US dollars 1.10 and 1.32 per household and water and sanitation between US dollars 1.39 and 1.52 per household.

Bangladesh↗

PubMed2003

Expression of the specific type IV phosphodiesterase gene PDE4B3 during different phases of long-term potentiation in single hippocampal slices of rats in vitro.

Hippocampal long-term potentiation (LTP), the most prominent cellular model for learning and memory formation, consists of phases: early-LTP (<4 h) and late-LTP (>4 h), with the latter dependent upon protein translation and transcription. To explore the molecular processes that might be specifically regulated during late-LTP, we have modified standard electrophysiological and molecular biological methods, which allowed the cloning of activated genes and their products from single hippocampal slices in vitro 8 h after LTP induction. From one such screen we identified a specific type IV phosphodiesterase gene, PDE4B3, the first cAMP-specific phosphodiesterase to be associated with LTP. Previous studies documented an integral role for the cAMP-PKA system in late-LTP and recently, inhibition of cAMP degradation facilitates LTP and ameliorates mnemonic deficits. We now report that PDE4B3 is modulated during LTP phases. Its activation is NMDA-receptor dependent and its transcription is transiently up-regulated 2 h after tetanization. Protein expression peaks 6 h after LTP induction and is rapidly down-regulated at 8 h, whereas cAMP levels decrease during LTP phases. Immunohistochemical studies identified that the majority of type IV phosphodiesterase protein staining is localized to the cell bodies and dendrites of neurones in hippocampal CA1.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells.

The relation between the consumption of cruciferous vegetables and reduced prostate cancer occurrence has been documented, although the responsible phytochemicals are unknown. The effects of sulforaphane (SFN) which occurs as the precursor glucosinolate in broccoli and other cruciferous vegetables, and its metabolite N-acetylcysteine conjugate (SFN-NAC) on prostate cancer cells were investigated. SFN and SFN-NAC were analyzed with the androgen-dependent human prostate cancer LNCaP cell line model. Cell growth and apoptosis were determined with the expression of androgen receptor and prostate specific antigen, DNA synthesis, cell cycle progression, DNA strand breaks and caspase activation to ascertain the effects and mechanism. SFN and SFN-NAC were demonstrated for the first time to mediate a dose-dependent apoptosis and growth arrest in the prostate cancer cells. Caspases were activated and DNA strand breaks were detected in apoptotic cells. The expression of phosphorylated and dephosphorylated androgen receptors, and the production of prostate specific antigen were attenuated. The expression of cyclin D1 and DNA synthesis were inhibited along with G1 cell cycle block, causing decreased cell density and growth. SFN and its metabolite SFN-NAC have similar activities to induce growth arrest and apoptosis, indicating that the effects of SFN are maintained through the metabolic processes. SFN as a dietary component of cruciferous vegetables active in the prevention of prostate cancer is discussed.

Anticarcinogenic Agents↗

PubMed2002

Performance of an extended aeration-microfiltration (EAM) reactor in treating high strength industrial wastewater.

A laboratory study was conducted on an Extended Aeration-Microfiltration (EAM) reactor in treating a food industry wastewater. The reactor contained horizontally laid hollow fibre microfiltration (MF) units that were fully submerged. The MF units were connected to a peristaltic pump that was used to extract permeate continuously under suction pressure. Continuous aeration from beneath the modules provided the crossflow effect to the MF units. Active activated sludge was used in the start-up where the sludge was mixed together with the feed water at a Food/Microorganisms (F/M) value of about 0.1. Primary effluent with Chemical Oxygen Demand (COD) values ranged between 1,500 and 3,000 mg/l was used as feed water. The EAM reactor was operated for nearly three months without initiating cleaning of the MF units. A suction pressure of 0.9 bar and Mixed Liquor Suspended Solids (MLSS) of over 5,500 mg/l were reached when nearing the end of the three month operation period. Permeate COD and turbidity reduction of over 97% and 99% respectively, were achieved. Prior to this, the MF module arrangements were studied; where vertically arranged modules were found to perform poorly as compared to the horizontally laid modules, in terms of clean water permeate flux.

Bioreactors↗

PubMed2001

Production of safe therapeutic feeds from contaminated water supplies.

We have assessed the effectiveness of using an osmotic sachet for safe rehydration of therapeutic milk from contaminated water supplies in a poor urban area of Bangladesh. 35 women were given sachets to hydrate in their homes and comparison of the hydration water and the reconstituted milk showed that the high bacterial contamination reported in the domestic water supply was removed by use of the sachet. The mean rehydration time was 4.5 h (range 3.4-5.5). This rehydration method could have a role in the preparation of therapeutic feeds where microbiological contamination of the environment is a serious problem and availability of adequate water is not a limiting factor.

Adult↗