Biomedical subjects

A Sadana

Publications and source records attributed to A Sadana.

At least 37 records · Page 2Linked to original sources

PubMed1998

Misuse of the London ambulance service: How much and why?

OBJECTIVES: To assess the degree of inappropriate use of the London Ambulance Service and analyse the reasons for misuse. DESIGN: An immediate assessment of the appropriateness of the "999" call by the ambulanceperson and casualty senior house officer followed by a retrospective review of each case by the accident and emergency (A&E) consultant. SETTING: A busy inner London A&E department. METHODS: Three hundred consecutive emergency ambulance arrivals to the A&E department underwent assessment as to the appropriateness of the call. RESULTS: Overall 53.7% of patients were considered justified in their call, 15.7% of calls were inappropriate, and in 19.0% of cases a unanimous decision was not reached. Eleven per cent of all forms were incompletely filled. CONCLUSIONS: Almost 16% of emergency ambulance calls were considered unanimously to be inappropriate. This suggests that 75,000 emergency calls per year to the London Ambulance Service are not necessary. The commonest reason for inappropriately calling an ambulance was that the caller felt that they had a serious or life threatening condition. The need for public education and deterrents of ambulance abuse are discussed. The further introduction of a nursing led triage "hot line" to appropriately dispatch ambulances according to clinical needs of the patient, and other alternatives to this are discussed.

Ambulances↗

PubMed1997

Binding Kinetics for Biosensor Applications Utilizing Fractals: A Categorization

Analyte-receptor binding reactions occurring on biosensor surfaces are categorized using a fractal analysis. Both a single- and a dual-fractal analysis are utilized to describe the analyte-receptor binding kinetics. The three categories presented to describe the binding kinetics include (a) case I-only a single-fractal analysis is utilized, (b) case II-a single- and a dual-fractal analysis are utilized (implying a change in the binding mechanism), and (c) case III-only a dual-fractal analysis is utilized. This is an initial attempt to categorize surface binding kinetics. The categorization provides one possible means of classifying analyte-receptor reactions occurring on biosensor surfaces. The analysis should help to improve biosensor performance parameters. The analysis is, in general, extendable to analyte-receptor reactions occurring on other surfaces.

Journal Article↗

PubMed1997

Influence of diffusion to fractal surfaces on the binding kinetics for antibody-antigen, analyte-receptor, and analyte-receptorless (protein) systems.

The diffusion-limited binding kinetics of antigen-antibody, ligand-receptor, analyte-receptorless systems for biosensor applications is analyzed within a fractal framework. The analysis presented applies equally well to these types of systems. For example, for the binding of 2-(p-toluidiny)-naphthalene-6-sulfonic acid (2,6-TNS) to beta-cyclodextrin (ligand-receptor system) immobilized on a fiber-optic base inclusate biosensor, an increase in temperature from 4 to 30 degrees C leads to an increase in the fractal dimension, D1 and to a decrease in the binding rate coefficient, k1. For the binding of TRITC-labeled low-density proteins (LDL) directly to an optical fiber-based sensor (analyte-receptorless system), an increase in the LDL concentration from 5 to 50 micrograms ml-1 in solution leads to a decrease in the fractal dimension, D1 and to an increase in the binding rate coefficient, k1. Also, during the binding of human chorionic gonadotropin (hCG) to anti-hCG antibody immobilized on a HPLC column (antigen-antibody system), an increase in temperature from 4 to 50 degrees C leads to an increase in the fractal dimension, D1 and in the binding rate coefficient. k1. The different examples analyzed and presented together for the three different types of systems provide one means of a 'unified analysis,' and a method by which the forward binding rate coefficient, k1 may be controlled, that is, by changing the fractal dimension or 'disorder' on the surface. The analysis should assist in improving the stability, sensitivity, and response time of biosensors wherein different types of binding systems are utilized in the analysis method. More-or-less all of the treatment presented should be applicable to the above types of binding systems occurring in non-biosensor applications also. However, the single-fractal analysis is unable to describe the data over the full time course of some of the experiments.

Antibodies↗

PubMed1997

Influence of Different Parameters on a Dual-Fractal Analysis for Antigen-Antibody Binding Kinetics for Biosensor Applications

The diffusion-limited binding kinetics of antigen (or antibody) in solution to antibody (or antigen) immobilized on a biosensor surface is analyzed within a fractal framework. The fit obtained by a dual-fractal analysis is compared with that obtained from a single-fractal analysis. In some cases, the dual-fractal analysis provides an improved fit when compared with a single-fractal analysis. This was indicated by the regression analysis provided by Sigmaplot (46). It is of interest to note that the state of disorder (or the fractal dimension) and the binding rate coefficient both increase as the reaction progresses on the biosensor surface. For example, for the binding of HIV-1 p24 in solution to monoclonal antibody (MAb) 18 covalently attached to a biosensor surface (49), an increase in the fractal dimension by 59% from a value of Df1 equal to 1.91 to Df2 equal to 2.95 leads to an increase in the binding rate coefficient by a factor of 15 from k1 equal to 21.1 to k2 equal to 339. Also, the binding of MAb 6301 and 6303 in solution to insulin growth factor binding protein-1 (IGFBP-1) covalently attached to the sensor surface is adequately described by a single-fractal analysis (48). The binding of MAb 6302 to IGFBP-1, however, requires dual fractals. This indicates a difference in the binding mechanisms of these MAbs. The different examples analyzed and presented together provide a means by which the antigen-antibody reactions may be better controlled by noting the magnitude of the changes in the fractal dimension and in the binding rate coefficient as the reaction progresses on the biosensor surface. Also, the magnitude of the changes in the binding rate coefficients (k1 and k2) and in the fractal dimensions (Df1 and Df2) as different parameters are changed for the different biosensor applications are of particular value.

Journal Article↗

PubMed1996

Antigen-antibody diffusion-limited binding kinetics for biosensors. A fractal analysis.

A fractal analysis is made for antigen-antibody binding kinetics for different biosensor applications available in the literature. Both types of examples are considered wherein: (1) the antigen is in solution and the antibody is immobilized on the fiberoptic surface, and (2) the antibody is in solution and the antigen is immobilized on the fiberoptic surface. For example, when the antibody is immobilized on the surface, an increase in the antigen Clostridium botulinum toxin A concentration in solution leads to (1) a decrease in the fractal dimension value or state of disorder, and (2) a higher rate constant for binding on the fiberoptic surface. An analysis of the effect of the influence of different parameters on the fractal dimension values for a particular example, such as varying treatments or incubation procedures, helps provide insights into the conformational states and reactions occurring on the fiberoptic surface. The analysis of the different example taken together provides novel physical insights into the state of "disorder" and reactions occurring on the surface. Such types of analysis should help contribute toward manipulating the reactions occurring on the fiberoptic surfaces in desired directions.

Antigen-Antibody Reactions↗

PubMed1996

Antigen-antibody binding kinetics for biosensors. Changes in the fractal dimension (surface roughness) and in the binding rate coefficient.

The diffusion-limited binding kinetics of antigen in solution to antibody immobilized on a biosensor surface is analyzed within a fractal framework. Changes in the fractal dimension, Df observed are in the same and in the reverse directions as the forward binding rate coefficient k. For example, an increase in the concentration of the isoenzyme human creatine kinase isoenzyme MB form (CK-MB) (antigen) solution from 0.1 to 50 ng/mL and bound to anti-CK-MB antibody immobilized on fused silica fiber rods leads to increases in the fractal dimension Df from 0.294 to 0.5080, and in the forward binding rate coefficient k from 0.1194 to 9.716, respectively. The error in the fractal dimension Df decreases with an increase in the CK-MB isoenzyme concentration in solution. An increase in the concentration of human chorionic gonadotrophin (hCG) in solution from 4000 to 6000 mIU/mL hCG and bound to anti-hCG antibody immobilized on a fluorescence capillary fill device leads to a decrease in the fractal dimension Df from 2.6806 to 2.6164, and to an increase in the forward binding rate coefficient k from 3.571 to 4.033, respectively. The different examples analyzed and presented together indicate one means by which the forward binding rate coefficient k may be controlled, that is by changing the fractal dimension or the "disorder' on the surface. The analysis should assist in helping to improve the stability, the sensitivity, and the response time of biosensors.

Antibodies↗

PubMed1996

An analysis of antigen-antibody binding kinetics for biosensor applications utilized as a model system: influence of non-specific binding.

The influence of non-specific binding on the specific binding of antigen in solution to antibody immobilized on a biosensor surface is presented for first-, one and a half-, second-, and other order reactions occurring under external diffusion-limited conditions. Both single-step and dual-step binding of antigen to antibody is considered. For a half-order reaction the value of the ratio of non-specific binding to specific binding (alpha) does not affect the rate of specific binding since a single curve represents the binding curve for alpha = 0 to 0.5. An increase in the alpha value leads to a decrease in the rate of binding and in the amount of antigen bound specifically to the antibody on the surface for first-, one and a half-, and second-order reactions. Also, an increase in the reaction order increases the sensitivity of the specific binding to the alpha value. An increase in the antigen concentration in solution increases the amount and the rate of specific binding for first-, one and a half-, and second-order reactions. The introduction of non-specific binding leads to complexities in the specific binding of the antigen for the one and half- and second-order reactions as the antibody concentration on the surface is varied. When non-specific binding is present there is an optimum value of the antibody concentration on the surface that yields the maximum rate and amount of antigen specifically bound for one and a half- and second-order reactions. Though this optimum amount of antibody immobilized on the surface is the same for the one and a half- and second-order reactions, it is different for different alpha values. No such complexities are observed for first-order reactions. The inclusion of non-specific binding in the analysis provides a more realistic picture of the binding of the antigen in solution to the antibody immobilized on the surface. The figures that show the numerically calculated binding rates for different orders when non-specific binding is present, represent the most useful part of the analysis for readers who are interested in constructing biosensors, and should assist in the control and manipulation of these interactions at the surface. These curves can be used to interpret a far from ideal binding of antigen to an immobilized antibody surface or vice versa. More-or-less all of the analysis should also be applicable to analytical systems that would not be classified as biosensors (that is, immuno and receptor assays).

Antibodies↗

PubMed1996

A fractal analysis of the influence of non-specific binding on antigen-antibody binding kinetics for biosensor applications.

A fractal analysis of the influence of non-specific binding on the specific binding of antigen in solution to antibody immobilized on a biosensor surface is presented for first-, one and a half-, second, and other-order reactions occurring under external diffusion-limited conditions. Both single-step and dual-step binding of antigen in solution to antibody immobilized on the surface is considered. For a first-order reaction, an increase in the fractal parameters, b, leads to a decrease in the amount of antigen in solution bound specifically to the antibody on the surface when non-specific binding is either absent or present. The presence of non-specific binding leads to a decrease in the amount of antigen bound to the antibody on the surface. For a one and a half- and for second-order reactions and when non-specific binding is either absent or present to a small degree (alpha = 0.01), an increase in the fractal parameter, b, leads to a decrease in the amount of antigen bound specifically to the antibody immobilized on the biosensor surface. However, for an alpha value of 0.1, the maximum rate and the amount of antigen bound specifically to the antibody immobilized on the biosensor surface is obtained for fractal parameter values of 0.2 and 0.4, and 0.4 for the one and a half- and for second-order reactions, respectively. Apparently, some amount of heterogeneity is helpful in obtaining the optimum amount and rate of antigen in solution bound specifically to the antibody on the surface for reaction orders higher than one. The applicability of the approach to real antibody surfaces is demonstrated.

Antigen-Antibody Reactions↗

PubMed1996

A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer.

To compare etoposide and etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) in maximizing the cost efficiency of care for patients with small cell lung cancer (SCLC), we obtained pharmacoeconomic data from a phase II randomized study of these agents. This clinical investigation assessed the efficacy and toxicity of etoposide phosphate combined with cisplatin in treating SCLC. In the economic analysis, we identified resources expended during chemotherapy and related concomitant procedures and matched them with the current procedure terminology level of costs for the provider and the payor. The valuation process was conducted in the specific point-of-care (outpatient v inpatient) setting. The appropriate pharmacoeconomic analytic tool used when comparators are considered to achieve equivalent clinical outcomes is cost-minimization analysis. We provide the cost-minimization analysis from two oncology care perspectives: the provider and the payor. In addition, a payor/ provider cost reduction model was constructed to illustrate the potential economic effects achieved through more efficient use of the outpatient chemotherapy facility due to the ease of administration of etoposide phosphate. The provider's average cost per patient for treating an SCLC patient for six cycles in US dollars is $26,764.48 for etoposide versus $26,026.70 for etoposide phosphate. The payor's average treatment cost per patient for treating an SCLC patient for six cycles for the respective regimens was $34,270.65 and $34,320.70. When the time savings associated with the etoposide phosphate regimen are applied to the outpatient chemotherapy facility, the adjusted average treatment costs per patient for the payor are $2,797.29 less than the costs for using the standard etoposide intravenous formulation. Delivering an etoposide phosphate regimen accrued adjusted savings of $2,897.03 per patient. Based on these results, etoposide phosphate is a superior pharmacoeconomic alternative compared with standard etoposide chemotherapy in managing SCLC. The potential increase in patient volume conferred by the relative simplicity of etoposide phosphate administration would have a significant impact on operations in terms of scheduling patients and staff and increasing operational efficiencies, thereby facilitating cost reductions in excess of $2,700 per patient when an etoposide phosphate regimen is chosen over an etoposide regimen.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Antigen-antibody diffusion-limited binding kinetics of biosensors: a fractal analysis.

A fractal analysis is made of antigen-antibody binding kinetics in various biosensor applications reported in the literature. Both sensor configurations are considered, wherein (a) the antigen is in solution and the antibody is immobilized on the fibre-optic surface, and (b) the antibody is in solution and the antigen is immobilized on the fibre-optic surface. For example, when the antigen is immobilized, an increase in the antibody concentration (anti-Ars) in solution leads to (a) an increase in the fractal dimension value and hence the state of disorder or roughness, and (b) a higher rate coefficient for binding on the fibre-optic surface. An analysis of the influence of different parameters on the fractal dimension values for a particular effect, such as a comparison of fresh and regenerated immunosensors, helps to clarify the conformational states and reactions occurring on the fibre-optic surface. Examination of the different cases presented together provides novel physical insights into the state of disorder or roughness on the surface. This research should contribute towards techniques for manipulating the reactions occurring on fibre-optic surfaces in desired directions.

Antigen-Antibody Reactions↗

PubMed1994

A fractal analysis of external diffusion limited first-order kinetics for the binding of antigen by immobilized antibody.

A fractal analysis of external diffusion limited first-order kinetics for the binding of antigen in solution by immobilized antibody on a fibre-optic biosensor indicates that as the fractal parameter (measure of "disorder" on the surface) increases the rate of binding and the amount of antigen bound to the antibody on the surface decreases. The fractal analysis and exponential type binding rate coefficients are used to analyze the influence of time-dependent binding rate coefficients on external diffusion limited kinetics. A decrease in the binding rate coefficients with time decreases the Damkohler number (decrease in the mass transfer limitations) leading to an increase in the rate of binding and the amount of antigen bound to the antibody on the surface, as expected. An increase in the (exponential) binding rate coefficient with time leads to unusual shapes of the binding curves. The time-dependent binding rate coefficients provide a more realistic picture of the binding of antigen in solution to the antibody covalently attached to the surface, and should assist in the control and manipulation of these interactions at the surface. A value of the fractal dimension of the surface of 2.96 to 2.97 obtained for our system characterizes the anomalies in the reaction-diffusion system and the heterogeneity of the surface.

Adsorption↗

PubMed1994

Protein inactivations during novel bioseparation techniques.

An analysis is presented for the quantitative and qualitative inactivation of proteins and other bioproducts during their separation utilizing the reverse micellar and the aqueous two-phase extraction techniques. Information on the influence of different parameters on the quantitative yields of the bioproducts separated is available, and more information is being gathered to provide further physical insights into improving the quantitative yields. However, very little information is available on the qualitative nature of the bioproducts separated utilizing either the reverse micelle or the aqueous two-phase extraction technique. More information is definitely required on the qualitative nature of the bioproducts separated by the above techniques to assist in their proper evaluation as effective bioseparation techniques.

Animals↗

PubMed1994

Efficiency and economics of bioseparation: some case studies.

An efficiency and economic analysis of the bioseparation of different bioproducts is presented by utilizing different case studies. Economic data on bioseparation processes is rarely presented in the open literature. The different examples presented together attempt to provide an overall framework for the cost structure involved in the different bioseparation processes. The models presented (Datar, 1986; Porter and Ladisch, 1992) provide novel insights into the cost structure of the different aspects of bioseparation processes. More studies are required that provide the insights necessary to assist in improving the efficiency and economics of bioseparation processes.

Biological Products↗

PubMed1992

Binding kinetics of antigen by immobilized antibody: influence of reaction order and external diffusional limitations.

The influence of reaction order and external mass transfer limitations on the binding kinetics of antigen in solution to antibody covalently or non-covalently attached to a cylindrical fiber-optic biosensor is presented. Both single-step and dual-step binding of antigen to antibody is considered. The rate of attachment of antigen to antibody is linear for all reaction orders in the time frame (100 min) considered. The rate of attainment of saturation levels of antigen in solution close to the surface is very rapid (within 20 min). An increase in the presence of mass transfer (denoted by a Damkohler number increase) decreases the saturation level of the antigen close to the surface, and the rate of antigen attachment to the antibody covalently or non-covalently bound on the surface for one-half, one, one and a half, and second-order reaction. As intuitively expected, an increase in the initial antigen concentration in solution increases the saturation level of the antigen close to the surface, and the rate of antigen attachment to the antibody covalently bound on the surface for all the reaction orders considered. Non-dimensional plots presented in the analysis help extend the analysis to different antigen-antibody systems. A decrease in the external diffusional limitations has an effect of decreasing the effect of reaction order on the saturation levels of antigen close to the surface and the rate of attachment of the antigen in solution to the antibody on the surface.

Antigen-Antibody Reactions↗

PubMed1992

Inactivation of proteins and other biological macromolecules during chromatographic methods of bioseparation.

The denaturation of proteins and other biological macromolecules such as gentamycin, mRNAs, and long-chain fatty acids during their separation by different chromatographic techniques is analyzed. Non-conventional techniques such as centrifugal partition chromatography are also examined. Particular attention is paid to the denaturing mechanisms prevalent under processing conditions, and how denaturation may perhaps be alleviated under laboratory conditions or during scale-up. The available mechanistic studies shed physical insights into the conformational behavior of proteins on chromatographic columns. Mechanistic studies of other biological macromolecule separation on columns is rare. Numbers for both recovery and purity of the biological product are presented wherever available. Scale-up studies are rare, nevertheless, those that are presented together do provide significant and valuable information, and may be generalized to other systems with caution.

Animals↗

PubMed1991

Bioseparation using affinity techniques.

Bioseparation of proteins from dilute solutions using different novel affinity procedures is reviewed. Emphasis is also placed on the quality of the product separated. Whenever possible, physical insights into the separation procedure are provided, besides indicating suitable directions where appropriate further research may be carried out. The procedures analyzed are different affinity chromatographic techniques, affinity separation using liquid perfluorocarbon supports, water soluble nonionic surfactants for affinity bioseparations, affinity cross-flow filtration, bioaffinity separation using reversed micelles, affinity precipitation and dual-functional affinity protein purification.

Cellulose↗

PubMed1990

Stability index for enzymes deactivating by different mechanisms.

A quantitative procedure for estimating changes in enzyme stability upon chemical modification is presented. Stability index for different deactivation mechanisms is presented and applied to different enzyme deactivations. The stability index provides a convenient method of estimating changes in enzyme stability upon chemical modification.

AMP Deaminase↗

PubMed1990

Protein/enzyme inactivation during different chromatographic methods of separation.

Protein denaturations encountered during the different types of chromatographic separations are presented. The analysis of different protein denaturations presented along with the causes of such denaturations provides a judicious framework to compare protein denaturations encountered by such separation techniques. Especially of interest are those studies which compare the mass recovery of proteins and the retention of activity by different chromatographic techniques. Reversed-phase chromatography is presented even though it is utilized nowadays only for specialized cases such as separation of small peptides. It appears that relatively mild interactions that are encountered generally in hydrocarbon-interaction chromatography are favorable to the preservation of the native (active) protein state. The few available mechanistic studies presented provide judicious physical insights into protein conformational behavior on chromatographic columns.

Animals↗