Neeti Sadana

Anesthetic management of a parturient with neuromyelitis optica

Women with neuromyelitis optica, an acute inflammatory demyelinating condition of the central nervous system, have an unpredictable clinical course in pregnancy. Providing neuraxial anesthesia for these patients is controversial, although relapses may occur after exposure to either general or neuraxial anesthesia and are common. We report the successful obstetric anesthesia management of a parturient with neuromyelitis optica, review the medical literature, and discuss specific considerations for obstetric anesthesia in patients with underlying demyelinating disease.

Medical Applications of Biosensors

The detection of analytes of medical relevance is yet another important area of biosensor applications. The ease of use of biosensors for the detection of analytes that are monitored especially for the onset of the different types of diseases as well as their management has led to the development of different types of biosensors. Some of these include sensitive immunoassay of tumor necrosis factor-α (TNF-α), novel microfluidic impedance assay for monitoring endothelin-induced cardiac hypertrophy, quartz-crystal microbalance-based immunosensor array for clinical immunophenotyping of acute leukemias, histone deacylase (HDAC) inhibitor assay based on resonance energy transfer, and biochip for a rapid and sensitive detection of multiple cancer markers simultaneously. This chapter analyzes examples of medical applications of biosensors and analyzes the kinetics of binding and dissociation of these examples using fractal analysis. Examples of biosensors discussed include the binding of TNF-α in solution to poly(guanine)-functionalized silica, the binding of different antigens in solution to the anti-CD antigen immobilized on a quartz-crystal microbalance (QCM) surface, the binding of 50 ng/mL myoglobin in serum to antimyoglobin antibody immobilized on a surface plasmon resonance (SPR) biosensor surface, the binding and dissociation of cardiomyocytes plus endothelin-1 (ET-1) with and without a DEP (dielectrophoresis) device, and the binding and dissociation of different concentrations of oxazaborolidine derivatives, BNO1, BNO2, BNO3, and BNO4 + 2 mM sucrose in solution to the enzyme FTF immobilized on a SPR biosensor chip surface.

Detection of Cancer Biomarkers by Biosensors: Part II

The kinetics of binding and dissociation of different cancer biomarkers to biosensor surfaces are analyzed.

Perioperative management of a parturient with antithrombin deficiency and the role of thromboelastography

65 Perioperative Management of a Parturient with Antithrombin Deficiency and the Role of Thromboelastography Abstract Type: Case Report/Case Series Neeti Sadana, M.D.; Lauren Sparks, M.D.; Daniel A. Biggs, M.D.; Abhinava S. Madamangalam, M.D. The University of Oklahoma Health Sciences CenterType: Case Report/Case Series Neeti Sadana, M.D.; Lauren Sparks, M.D.; Daniel A. Biggs, M.D.; Abhinava S. Madamangalam, M.D. The University of Oklahoma Health Sciences Center Antithrombin (AT, formerly ATIII) is a serine protease inhibitor that plays an essential role in hemostasis. Its mechanism of action is to inactivate thrombin and coagulation factors IXa, Xa, XIa, and XIIa (1). Hereditary AT deficiency is a rare autosomal dominant coagulopathy that significantly increases the risk of thromboembolic phenomenon, especially during pregnancy and the puerperium. In the absence of anticoagulation, the risk of thrombosis is as high as 70%(2). There is a paucity of literature regarding the use of thromboelastography(TEG)to guide anesthetic management in patients with AT deficiency. Previous case reports describe the use of anticoagulation and nonpharmacologic techniques for pain management during labor and vaginal delivery (3). One case describes the use of an epidural for cesarean delivery as the patient reported an adverse reaction to general anesthetic medications (4). Our patient was placed on low molecular weight heparin (LMWH) throughout pregnancy to prevent thrombotic complications at a dose of 1.5 mg/Kg. LMWH was stopped 24 hours prior to scheduled cesarean delivery for breech presentation, and she was placed on Thrombate III (purified human AT concentrate) as replacement. Thrombate III was recommended by her hematologist to reduce intra and post-operative thrombotic complications by raising the AT level to 80-100% of normal. The use of this drug has been associated with hematoma formation and increased bleeding risk (5). The patient desired a regional anesthetic for her operative delivery. We were uncertain as to the effects of Thrombate III on coagulation and therefore decided to utilize TEG to aid in management. Baseline TEG and platelet mapping were performed which revealed normal clot strength, adequate platelet number and no platelet inhibition. Thrombate III was then given and a repeat TEG was performed. The patient was hypercoagulable ( K= 1.2; G=15.1; Alpha =73.7) despite excessively high levels of antithrombin 3 (>200%). It is possible that she also had Protein C or S deficiency that was unknown. The patient was counseled about the risks of thrombosis versus bleeding and spinal hematoma formation. The patient then requested general endotracheal anesthesia which was performed without complication. A baby with APGARS of 9 and 9 was delivered by cesarean. Blood loss intra-operatively was minimal. A TEG was performed 24 hours post-operatively and the patient was still hypercoagulable. Hematology work-up in the postpartum period was negative for new findings. This case highlights the potential challenges of managing parturients with rare disorders of coagulation and the use of TEG and platelet mapping to guide anesthetic decisions. 1. Rodgers G. Thromb Haemo 2009:101:806-812 2. Hellgren M. Gynecol Obstet Invest 1982:14:127-41 3. Yamada T. Obstet and Gynaecol Res 2001:27:189-97 4. Rowbottom SJ. Anaesthesia Intens Care 1995:23:493-95 5. Brouwer JL.Thromb Haemo 2009:101:5-6

Biosensors Involved in Drug Discovery

Drug discovery is an important area of investigation for biosensor applications. The identification of appropriate drugs from a wide spectrum of possible drug candidates can consume tremendous amounts of time and resources. Biosensors can significantly shorten this time and also help minimize the resources required to help identify suitable drug candidates. This chapter provides examples where biosensors have been used for drug discovery and describes fractal analysis for binding kinetics of these examples. The binding kinetics is described by either a single- or dual-fractal analysis, and it is an important area of investigation wherein there is a continually increasing application of biosensors, and where biosensors are making important contributions. This is particularly so for cases wherein biosensors may be used as an HTS method to quickly narrow down the possible suitable candidates from a wide spectrum of potential candidates. The fractal dimension provides a quantitative measure of the degree of heterogeneity present on the biosensor chip surface. The examples analyzed in this chapter include inhibitors of protein kinases wherein the interactions of ARC and isoforms of the catalytic subunit (Ca) of CAPK are examined, the binding of phosphate ion (Pi) to a rhodamine-PBP fluorescence-based phosphate biosensor, and the binding of different concentrations (in mU) of MET-AMC and methionine in solution in the cSPA charging assay. The examples presented in this chapter emphasize that the degree of heterogeneity that exists on the biosensor surface does significantly affect, in general, the rate coefficient and affinity values and subsequently the kinetics in general.

Biosensor Performance Parameters and their Enhancement

The areas of biosensor application are increasing continuously and biosensor research is gradually becoming an established area of widespread usage. One aspect of biosensor application that needs careful study is the enhancement of biosensor performance parameters. Quite often, researchers especially in the academic arena are content with developing a biosensor for a novel application. Little interest and few resources are expended on the ways and means of improving biosensor performance parameters such as sensitivity, reproducibility, validation, enhanced response, stability, improvement in resolution, detection time, limit of detection, etc. The industrial sector, which is under constant pressure due to intense competition to improve biosensor performance parameters is particularly interested in this area of biosensor development. One recognizes that if modifications are made for the biosensor to enhance a particular performance parameter, then it is quite possible that another biosensor parameter may exhibit a decrease in its performance characteristic. For example, if one enhances the sensitivity of a biosensor by some type of modification, then perhaps it is quite possible that after this modification, the biosensor may exhibit a decrease in its stability characteristic. It would be useful to relate the biosensor performance parameter(s) to a common variable, such as the degree of heterogeneity or fractal dimension of the biosensor surface. Then, by changing the degree of heterogeneity to help improve a particular biosensor performance parameter, one does have a priori an estimate of the influence of this change in heterogeneity on other biosensor performance parameters. However, practical experience as against the theoretical exploration in the biosensor R&D field is irreplaceable as far as improving biosensor performance parameters are concerned.

Binding and Dissociation of Biomarkers for Alzheimer's Disease on Biosensor Surfaces

Dementia is a loss of brain function that may occur with certain diseases. Alzheimers disease (AD) is one form of dementia. AD worsens with time, and it affects memory, thinking, and behavior (PubMed Health, 2011). These authors indicate that as one grows older the risk of developing AD goes up. These authors emphasize that AD is not a part of the normal aging process. The risk of AD increases if a close blood relative (such as a brother, sister, or parent) has it. These authors further indicate that AD may be characterized as early onset and late onset. Early onset of AD occurs before 60 years of age, and late onset of AD develops in people of 60 years of age and older. AD may be briefly described in undergoing three stages: (1) early symptoms (misplacing items, getting lost in familiar routes, etc.), (2) “intermediate stage” symptoms (forgetting details about current events, difficulty in reading and writing, etc.), and (3) severe AD symptoms (can no longer understand language, recognize family members, or perform daily living activities).

Binding and Dissociation of Biomarkers for Systemic Lupus Erythematosus

A fractal analysis is presented for the kinetics of binding and dissociation of systemic lupus erythematosus (SLE) biomarkers and other autoimmune diseases on biosensor surfaces. For example, the biomarker tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine is presented and the kinetics of binding to a single-molecule nanoparticle optical biosensor (SMOBS) is analyzed.

A Fractal Analysis of Biomarkers for Different Diseases on Biosensor Surfaces

The kinetic analysis of the binding and dissociation of different diseases is presented. Fractals are used. Some of the biomarkers using biosensors include Hepcidin, apoliprotein human myoglobin and human interferon gamma (hIFNγ). The analysis should provide a better understanding of the applications of these and other similar biomarkers which would lead to a better prognosis of diseases.

A Fractal Analysis of Binding and Dissociation of Glucose to Different Biosensor Surfaces

In the previous chapter, the detection of glucose by biosensors and the kinetics of binding and dissociation by different biosensors were presented. Since diabetes is such a prevalent disease and has reached almost epidemic proportions in the United States and throughout the world, it is worthwhile to present another chapter on the detection of glucose by different biosensors. These articles have appeared in recent literature. One should remember that the detection of glucose was the first application of biosensors. Since then, of course, there have been tremendous advancements in the detection of glucose by different biosensors.