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Biomedical subjects

S Ahmad

Publications and source records attributed to S Ahmad.

At least 91 records · Page 5Linked to original sources
PubMed2000

New ultrasound approaches to dialysis access monitoring.

The failure of dialysis access is a frequent source of morbidity and hospitalization. Traditional methods of graft surveillance include: (1) clinical examination, (2) venous line pressure measurements during dialysis, (3) urea or tracer recirculation measurement, (4) continuous wave (CW) Doppler methods, (5) duplex ultrasonography, and (6) radiograph angiography. All these methods require special training and/or laboratory tests. The purpose of this study was to test a simple continuous-wave Doppler method that could be applied to measure the flow rate in dialysis access every time the patient undergoes dialysis. Twenty dialysis patients, 15 with polytetrafluoroethylene grafts and 5 with arteriovenous fistulae, were studied. Two hundred fifty-three examinations were performed over an 8-month period. Doppler waveforms of the access flow were obtained with the pump on, with the pump off, and with the pump on again. Systolic and diastolic Doppler frequency measurements were made, and the pump-on and pump-off measurements were compared. In an access functioning normally, the Doppler frequencies are higher with the pump off than with the pump on. In 22% of the cases, there were abnormal findings in which the Doppler frequencies were lower with the pump off than with the pump on. This occurs if the needles are incorrectly placed, suggesting that recirculation is occurring. Recirculation also occurs if there is stenosis of the access. Examining the hemodialysis access during each dialysis session with an inexpensive directional Doppler may identify a significant stenosis and improve the efficiency of dialysis by detecting those patients in whom the arterial and venous needles are reversed.

Adult↗
PubMed2000

Dialysate made from dry chemicals using citric acid increases dialysis dose.

A new dry dialysate concentrate acidified with citric acid (citrate dialysate) has been used in two separate clinical studies of hemodialysis patients. The first compared a single treatment using this dialysate, with one dialysis using regular standard dialysate acidified with acetic acid (regular dialysate) in a prospective, randomized, crossover study of 74 dialyses. Changes in blood levels of electrolytes and other blood constituents during dialysis were calculated by subtracting postdialysis from predialysis blood concentrations. Compared with acetic acid dialysate, citrate dialysate was associated with significantly greater decreases in total and ionized calcium, magnesium, and chloride levels. Citrate dialysate was also associated with greater increases in serum sodium and citrate concentrations, although their postdialysis concentrations remained within or just outside normal ranges. Changes in other blood constituents were similar with both dialysates. The second study used citrate dialysate exclusively for all dialyses over a 12-week period in 25 patients. Predialysis blood samples were drawn at the start of the study and at 4-week intervals thereafter, and postdialysis blood samples were obtained after the first and last dialysis. Repeated-measure analysis showed that although predialysis blood concentrations of magnesium, potassium, and citrate remained within the normal range, there was a significant declining trend over the course of the study. At the same time, predialysis serum bicarbonate levels increased, and significantly more patients had a predialysis bicarbonate concentration within the normal range at the end of the study than at the start (15 versus 8 patients; P = 0.001, chi-square). In 19 patients (excluding 3 patients for whom the type of dialyzer was changed during the study), the dose of dialysis for the first and last dialysis was calculated by urea reduction ratio and Kt/V. There was a significant increase in both measurements without changes in dialysis time, blood and dialysate flows, or dialyzer used. The urea reduction ratio increased from 68% +/- 5.9% to 73% +/- 5.3% (P < 0. 03), and the Kt/V from 1.23 +/- 0.19 to 1.34 +/- 0.20 (P = 0.01) from the first to last dialysis, respectively. In conclusion, this citric acid dialysate was well tolerated, and intradialytic changes in blood chemistries were similar to those seen with regular dialysate. Using dialysate containing citric instead of acetic acid increases the delivered dialysis dose.

Adult↗
PubMed2000

Two new diterpenoids from Salvia triloba.

Two new diterpenoids, trilobic acid (1) and trilobiol (2), have been isolated from the methanolic extract of Salvia triloba. Their structures were elucidated with the aid of NMR spectroscopy including two-dimensional-NMR techniques.

Diterpenes↗
PubMed2000

Characterization of rpoB mutations in rifampin-resistant Mycobacterium tuberculosis isolates from the Middle East.

The nature and frequency of mutations in the rpoB gene of rifampin-resistant clinical Mycobacterium tuberculosis isolates vary considerably according to geographical locations. There is no information on the prevalence of specific mutations in clinical M. tuberculosis strains isolated from patients in Middle-Eastern countries. In this study, 13 rifampin-resistant and 6 susceptible clinical M. tuberculosis isolates were tested for identification and characterization of mutations in the rpoB gene by INNO-LiPA Rif. TB kit and DNA sequencing of the PCR amplified target DNA. The kit identified all six susceptible strains as rifampin-sensitive and the DNA sequence of the amplified rpoB gene in the target region matched perfectly with the wild-type sequence. The kit identified 12 resistant isolates as rifampin-resistant with specific detection of mutations in 8 isolates while one of the rifampin-resistant strain was identified as rifampin-susceptible. DNA sequencing confirmed these results and, in addition, led to the specific detection of mutations in 4 rifampin-resistant isolates in which specific base changes within the target region could not be determined by the INNO-LiPA Rif. TB kit. The majority (8 of 13) of resistant isolates involved base changes at codon 531 of the rpoB gene. Mutations at codon position 531 within the rpoB gene have also been reported in majority of rifampin-resistant strains from Greece and St. Petersburg, Russia but not from other geographical locations.

Antibiotics, Antitubercular↗
PubMed2000

Potential of rice husks for antimony removal.

The adsorption behavior of rice husks for antimony ions from aqueous solutions has been investigated as a function of appropriate electrolyte, equilibration time, hydrogen ions, amount of adsorbent, concentration of adsorbate, effect of diverse ions and temperature. The best conditions in which this material can be used as adsorbent have been explored. The radiotracer technique was employed to determine the distribution of antimony (122Sb) using a batch method. Maximum adsorption was observed at 0.01 mol L(-1) acid solutions (HNO3, HCl, H2SO4 and HClO4) using 1.0 g of adsorbent for 1.92 x 10(-5) mol L(-1) antimony concentration in 10 min equilibration time. Studies show that the adsorption decreases with the increase in the concentrations of all the acids. The adsorption data follow the Freundlich isotherm over the range of 1.92 x 10(-5) to 2.05 x 10(-4) mol L(-1) antimony concentration. The characteristic Freundlich constants i.e., 1/n = 0.82 +/- 0.05 and K = 4.61 +/- 0.07 m mol g(-1) have been computed for the sorption system. The uptake of antimony increases with the rise in temperature (299-323 K). Thermodynamic quantities i.e., deltaG0, deltaS0 and deltaH0 have also been calculated for the system. The sorption process was found to be endothermic.

Journal Article↗
PubMed2000

Enhanced safety and efficacy of live attenuated SIV vaccines by prevaccination with recombinant vaccines.

The only vaccines shown to be protective against intravenous challenge with virulent virus in the simian immunodeficiency virus (SIV)/macaque model are attenuated live SIVs. However, these vaccines have several disadvantages: 1) they persist indefinitely in vaccinated macaques; 2) they are pathogenic to neonatal macaques; and 3) they are lethal in some adult macaques. To enhance the safety and efficacy of these vaccines, we immunized macaques first with recombinant vaccines and then inoculated the animals with SIV(delta(nef)). In the first experiment, preimmunized macaques advanced to disease slower than controls after challenge with virulent SIV; five animals survived for 3 years without disease and only the vaccine virus (SIV(delta(nef)) could be isolated at this time. In the second experiment, preimmunized animals had lower virus loads and no disease compared to controls.

Animals↗
PubMed2000

Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids.

One of the key molecules promoting angiogenesis is the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF or VEGF-A), which acts through two high-affinity receptor tyrosine kinases (VEGFR), VEGFR-1 (or Flt-1) and VEGFR-2 (or KDR/Flk-1). It was shown before that a soluble variant of VEGFR-1 (sVEGFR-1) can be generated by differential splicing of the flt-1 mRNA. This soluble receptor is an antagonist to VEGF action, reducing the level of free, active VEGF-A, and therefore, plays a pivotal role in the generation of vascular diseases like pre-eclampsia or intra-uterine growth retardation. Here we show that sVEGFR-1 is produced by cultured human microvascular and macrovascular endothelial cells and a human melanoma cell line. The soluble receptor is mainly complexed with ligands; only 5-10% remains detectable as free, uncomplexed receptor protein. Furthermore, we show the time course of total and free sVEGFR-1 release together with its putative ligands, VEGF-A and placenta growth factor (PIGF), from macrovascular endothelial cells. The release of sVEGFR-1 was quantitatively measured in two different ELISA types. The release of sVEGFR-1 was strongly enhanced by phorbol-ester (PMA); the cells produced up to 22 ng/ml of sVEGFR-1 after 48 hours. The expression of VEGF-A and PIGF was moderately influenced by PMA. We also show a hypoxia-induced increase of sVEGFR-1 expression in cells cultured from placenta, a tissue that has a high flt-1 gene expression. Moreover, we demonstrate that sVEGFR-1 in amniotic fluids acts as a sink for exogenous VEGF165 and PIGF-2. Here, for the first time, to what extent recombinant ligands have to be added to compensate for the sink function of amniotic fluids was analyzed. In conclusion, human endothelial cells produce high levels of sVEGFR-1, which influences the availability of VEGF-A or related ligands. Therefore, sVEGFR-1 may reduce the ligand binding to transmembrane receptors and interfere with their signal transduction.

Body Fluids↗
PubMed2000

Saccharococcus caldoxylosilyticus sp. nov., an obligately thermophilic, xylose-utilizing, endospore-forming bacterium.

Several closely related, xylanolytic, thermophilic bacilli were isolated from local soils on xylose-containing minimal medium. On the basis of morphology and biochemical characteristics, one of the isolates, designated strain S1812T (T = type strain), was studied further. Strain S1812T was a xylanolytic, sporulating, Gram-positive, rod-shaped bacterium. Its Gram-positive nature was confirmed by electron microscopic examination of thin sections of the cells. The isolate was a thermophilic (optimum temperature for growth, 65 degrees C), facultative anaerobe that grew on a wide range of carbon sources including glucose, lactose, starch and xylose. It expressed high levels of both xylose isomerase and xylulokinase on xylose and also on glucose. The DNA G + C content was 44 mol%. rRNA gene sequence analysis placed strain S1812T in Bacillus cluster 5; it was more closely related to Saccharococcus thermophilus than to thermophilic Bacillus species. DNA-DNA hybridization also indicated its close relationship to S. thermophilus. Based on the evidence presented, it is proposed that strain S1812T be designated Saccharococcus caldoxylosilyticus sp. nov. Strain S1812T is the type strain (= ATCC 700356T = DSM 97-987T).

Base Composition↗
PubMed2000

Phylogenetic analysis of gram-positive bacteria based on grpE, encoded by the dnaK operon.

The dnaK operon in gram-positive bacteria includes grpE, dnaJ and, in some members, hrcA as well. Both DnaK and DnaJ have been utilized for constructing phylogenetic relationships among various organisms. Multiple copies exist for dnaK and dnaJ genes in some bacterial genera, as opposed to a single gene copy for grpE and for hrcA, according to the currently available data. Here, we present a partial protein-based phylogenetic tree for gram-positive bacteria, derived by using the amino acid sequence identity of GrpE; the results are compared with the phylogenetic trees generated from 5S rRNA, 16S rRNA, dnaK and dnaJ sequences. Our results indicate three main groupings: two are within low-G+C DNA gram-positive bacteria comprising Bacillus species and Staphylococcus aureus on the one hand and Streptococcus species/Lactococcus lactis/Enterococcus faecalis/Lactobacillus sakei on the other hand; the Mycobacterium species and Streptomyces coelicolor, belonging to the high-G+C DNA gram-positive bacteria, form the third cluster. This hierarchical arrangement is in close agreement with that obtained with 16S rRNA and DnaK sequences but not DnaJ-based phylogeny.

Amino Acid Sequence↗
PubMed2000

Beam-commissioning methodology for a three-dimensional convolution/superposition photon dose algorithm.

Commissioning beam data for the convolution/superposition dose-calculation algorithm used in a commercial three-dimensional radiation treatment planning (3D RTP) system (PINNACLE(3), ADAC Laboratories, Milpitas, CA) can be difficult and time consuming. Sixteen adjustable parameters, as well as spectral weights representing a discrete energy spectrum, must be fit to sets of central-axis depth doses and off-axis profiles for a large number of field sizes. This paper presents the beam-commissioning methodology that we used to generate accurate beam models. The methodology is relatively rapid and provides physically reasonable values for beam parameters. The methodology was initiated by using vendor-provided automodeling software to generate a single set of beam parameters that gives an approximate fit to relative dose distributions for all beams, open and wedged, in a data set. A limited number of beam parameters were adjusted by small amounts to give accurate beam models for four open-beam field sizes and three wedged-beam field sizes. Beam parameters for other field sizes were interpolated and validated against measured beam data. Using this methodology, a complete set of beam parameters for a single energy can be generated and validated in approximately 40 h. The resulting parameter values yielded calculated relative doses that matched measured relative doses in a water phantom to within 0.5-1.0% along the central axis and 2% along off-axis beam profiles for field sizes from 4 cmx4 cm to the largest field size available. While the methodology presented is specific to the ADAC PINNACLE(3) treatment planning system, the approach should apply to other implementations of the dose model in other treatment planning system.

Algorithms↗
PubMed2000

Hypoxia induces hexokinase II gene expression in human lung cell line A549.

During adaptation to hypoxic and hyperoxic conditions, the genes involved in glucose metabolism are upregulated. To probe involvement of the transcription factor hypoxia-induced factor-1 (HIF-1) in hexokinase (HK) II expression in human pulmonary cells, A549 cells and small-airway epithelial cells (SAECs) were exposed to stimuli such as hypoxia, deferoxamine (DFO), and metal ions. The largest increase in HK-II (20-fold for mRNA and 2.5-fold for enzymatic activity) was observed in A549 cells when exposed to DFO. All stimuli selectively increased the 5.5-kb rather than 4-kb transcript in A549 cells. Cycloheximide and actinomycin D inhibited these responses. In addition, cells were transfected with luciferase reporter constructs driven by the full-length HK-II 5'-regulatory region (4.0 kb) or various deletions of that region. A549 cells transfected with the 4.0-kb construct and exposed to hypoxia or DFO increased their luciferase activity 7- and 10-fold, respectively, indicating that HK-II induction is, at least in part, due to increased gene transcription. Sixty percent of the inducible activity of the 4.0-kb construct was shown to reside within the proximal 0.5 kb. Additionally, cotransfection with a stable HIF-1 mutant and the 4.0-kb promoter construct resulted in increased luciferase activity under normoxic conditions. These results strongly suggest that HK-II is selectively regulated in pulmonary cells by a HIF-1-dependent mechanism.

Cell Line↗
PubMed2000

Soluble P-selectin in human plasma: effect of anticoagulant matrix and its levels in patients with cardiovascular disorders.

P-Selectin represents a cell surface glycoprotein that is constitutively present in the Weibel-Palade bodies of endothelial cells and in the alpha-granules of platelets. In inflammation and thrombogenic conditions, plasmatic P-selectin levels are markedly elevated, indicating the leakage of this marker from these sites. In this study, a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) utilizing a monoclonal soluble P-selectin (sP-selectin) antibody was employed to assess this marker in blood samples collected in various anticoagulants such as heparin, hirudin, sodium citrate (3.2% and 3.8%), and ethylenediaminetetraacetic acid (EDTA). The soluble P-selectin levels ranged from 26 ng/mL to 44 ng/mL. Sodium citrate (3.8%) was used to collect platelet-poor plasma (PPP) from patients with heparin-induced thrombocytopenia (HIT), coronary angioplasty (CA), or coronary atherectomy (CAT). In comparison with the control group (approximately 30 ng/mL), all of these patient groups showed a marked elevation of sP-selectin levels (HIT = 96 ng/mL [n = 18], CA = 46 ng/mL [n = 6] and CAT = 60 ng/mL [n = 10]). In platelet-rich plasma (PRP) preparations using various anticoagulants, the sP-selectin levels were markedly higher, ranging from 87 ng/ mL to 117 ng/mL (n = 10). In patients recruited into a clinical trial (the argatroban [ARG] 911 Study), in which argatroban was used as an alternate anticoagulant in patients with HIT, a 25% to 35% decrease in sP-selectin levels was observed after 72 hours of argatroban treatment. In addition, the relative ratio between levels in PRP and PPP in these patients differed, suggesting that the anticoagulant matrix influences the sP-selectin levels. These data clearly suggest that the anticoagulant matrix and blood collection procedures may significantly influence the plasmatic P-selectin levels. Furthermore, in different clinical conditions, elevation of this marker may reflect endogenous platelet activation; however, optimal anticoagulant for blood collection is important for proper diagnostic validation.

Adult↗
PubMed2000

Pathophysiology of heparin-induced thrombocytopenia. Clinical and diagnostic implications--a review.

OBJECTIVE: This review of heparin-induced thrombocytopenia (HIT), the most frequent and dangerous side effect of heparin exposure, covers the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of this disease syndrome. DATA SOURCES AND STUDY SELECTION: Current consensus of opinion is given based on literature reports, as well as new information where available. A comprehensive analysis of the reasons for discrepancies in incidence numbers is given. The currently known mechanism is that HIT is mediated by an antibody to the complex of heparin->platelet factor 4, which binds to the Fc receptor on platelets. New evidence suggests a functional heterogeneity in the anti-heparin-platelet factor 4 antibodies generated to heparin, and a "superactive" heparin-platelet factor 4 antibody that does not require the presence of heparin to promote platelet activation or aggregation has been identified. Up-regulation of cell adhesion molecules and inflammatory markers, as well as preactivation of platelets/endothelial cells/leukocytes, are also considered to be related to the pathophysiology of HIT. Issues related to the specificity of currently available and new laboratory assays that support a clinical diagnosis are addressed in relation to the serotonin-release assay. Past experience with various anticoagulant treatments is reviewed with a focus on the recent successes of thrombin inhibitors and platelet GPIIb/IIIa inhibitors to combat the platelet activation and severe thrombotic episodes associated with HIT. CONCLUSIONS: The pathophysiology of HIT is multifactorial. However, the primary factor in the mediation of the cellular activation is due to the generation of an antibody to the heparin-platelet factor 4 complex. This review is written as a reference for HIT research.

Heparin↗
PubMed2000

Pharmacokinetics of argatroban in primates: evidence on endogenous uptake.

BACKGROUND: Antithrombin agent, argatroban, is currently undergoing several clinical trials for cardiovascular indications. Because of its solubility, this drug is usually administered via an intravenous bolus followed by infusion. The purpose of this study was to determine the pharmacokinetics of argatroban after intravenous bolus injection in primates. METHODS: Parallel in vitro studies in primate whole blood were carried out to simulate a one-compartment system. Argatroban (range 1.0-7.5 mg/kg) was administered to four groups of primates and blood samples were drawn at various time periods. Argatroban measurements were made in plasma using functional (aPTT, Heptest, TT) and HPLC methods. RESULTS: In vitro, argatroban primarily distributed in the plasma in proportionate amounts. Relative uptake of argatroban to the blood cells (leukocytes and erythrocytes) was minimum. However, in vivo, argatroban followed a complex pharmacokinetics. Within 5 min after the bolus administration, only <20% of argatroban was recovered. The recovered amount was proportionate to the dosage and followed the expected kinetics with a half-life of <20 min. Simultaneous quantitation of M1-metabolite of argatroban revealed only a fraction of recovered argatroban (approximately 25%) converted into M1 in these experimental settings. Results obtained from the functional and absolute methods correlated well. HPLC profile did not reveal the presence of any other metabolite(s). CONCLUSIONS: These observations suggest that argatroban may be endogenously taken up by the vascular or other sites and may exhibit a complex kinetics. In acute settings, the metabolic transformation of argatroban to M1 is relatively low. To further clarify the pharmacokinetics/pharmacodynamics of this drug, additional studies are warranted.

Animals↗
PubMed2000

A study of communication in the Cardiac Surgery Intensive Care Unit and its implications for automated briefing.

We present a study of the information transferred among caregivers in the context of cardiac surgery and use the study to evaluate a system, MAGIC, that we are developing for automated generation of briefings. Our framework integrates cognitive and quantitative evaluation methods and features three standards that reflect current practice in the Cardiothoracic Intensive Care Unit (CTICU). Using experimental design to compare human-generated and machine-generated briefings, we show that MAGIC's current level of performance is useful. Moreover, MAGIC could help improve information flow in the CTICU by providing a consistent set of information earlier than in current practice. The separate standards are also consistent in suggesting specific modifications that may be necessary for iterative design and further system development.

Communication↗
PubMed1999

Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and beta-chemokine production.

Immunization with live attenuated simian immunodeficiency virus (SIV) strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model. To better understand the role that CD4(+) T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains. Macaques chronically infected with live attenuated SIV had strong proliferative responses to SIV proteins, with stimulation indices of up to 74. The magnitude of the proliferative response to SIV Gag varied inversely with the degree of attenuation; Gag-specific but not envelope-specific responses were lower in animals infected with more highly attenuated SIV strains. SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-gamma, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta but not IL-4 or IL-10. Intracellular flow cytometric analysis documented that, in macaques vaccinated with SIVmac239Deltanef, up to 2% of all CD4(+)T cells were specific for SIV p55. The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this vaccination approach to generate protection against challenge with wild-type SIV.

Animals↗