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US 5932207 A Abstract An active ingredient complex to promote the growth of cells, tissue and/or organs is disclosed. The complex comprises the following form ingredients: a structural component, a recruiting component, an adhesion component and an adherence component.
Claims(8) 1. A complex for the growth of bony tissue or bone comprising:
a bone derived structural component comprising a macromolecular three-dimensional matrix derived from bone-specific proteins; at least one bone derived chemotactic component for recruiting bone growth cells to said matrix; at least one bone derived adhesion component for adhering said cells to said matrix, wherein said adhesion component binds to said protein matrix and to specific receptors of said bone growth cells; and at least one bone derived bone growth factor. 2. The complex of claim 1, wherein said adhesion component is selected from the group consisting of fibronectin, tenascin, cytotactin, laminin, chondroinectin, collagen types IV, V, VII, N-CAM, L-CAM, and integrin.
3. The complex of claim 1, wherein said growth factor is taken from the group consisting of fibroblast growth factor and transforming growth factor-beta.
4. The complex of claim 1, wherein said chemotactic component is identifiable by a chamber with a porous filter.
5. The complex of claim 1, wherein said chemotactic component comprises a peptide.
6. The complex of claim 1, wherein said chemotactic component is water soluble.
7. The complex of claim 1, wherein said adhesion component is water insoluble.
8. The complex of claim 1, wherein said growth factor is bound to said structural component.
Description This is a continuation of application Ser. No. 07/849,083 filed on Sep. 17, 1992 (now abandoned) which is a 371 of PCT/DE90/00782 filed on Oct. 12, 1990. The various functional performances of living organisms (human beings, animals, plants) are usually not diffused over their bodies, but rather are separate and are concentrated according to a characteristic structural and functional plan for each individual type of function taking place in a distinct biological part. These biological parts, the subject of the invention, include organelles, cells, tissue, organs, and parts thereof. Frequently these parts are then combined into complex systems to which the invention likewise makes reference. Examples of such biological parts are muscle tissue, cartilage, bone, liver, spleen, skin, etc. Examples of complex systems are the nervous system, vascular system, skeletal system, hormone system, immune system, etc. In the course of life and likewise in the formation of the living organism, any living being can be subject to damages of structure and function of individual biological parts up to the point that the part or even the entire system can be completely nonfunctional. This functional failure could among other things be of genetic origin or it could occur because microorganisms such as bacteria, viruses, funguses or parasites have damaged or destroyed the biological parts, because injuries have occurred due to mechanical, chemical, thermal, electric or radiological effects, or because disorders of unknown origin have had an effect on the biological parts in the form of various degenerative processes, cancer or many types of modifications due to age. The present state of the art is to try to compensate for damages or even for complete loss of function of individual biological parts by application of chemical compounds. In doing so, a deficiency of function or the complete lack of function or functional effectiveness of individual metabolic products which are produced by the relevant biological part is to be compensated. One example of this is the loss of the function or some part of the function of the pancreas, which leads to an insulin deficiency or to a complete failure of the product synthesis of the pancreas. Insulin obtained from animals or produced chemically or biotechnically is used to compensate for the deficiency. This manner of use of chemical compounds or biological synthesis products can only partially compensate for the insufficient performance of functions of biological parts, because only short-term effective deposits of the compound can be placed in the body and there is no regulated release of the materials or synthetic materials into the body to fulfill the instant requirement of the body. Because of these problems, and especially in the case of the occurrence of damages to a plurality of functional parts or in the case of destruction of an entire biological part, the state of the art also includes the integration of the often life-vital defective or lost functional parts into a technical apparatus and to attach the apparatus to the body or to build it into the body as a prosthesis. Some examples of such auxiliary means in extracorporal use are spectacles, hearing aids, arm or leg prostheses, synthetic kidneys, etc. For intracorporal use, heart pacemakers, blood vessel prostheses, synthetic joints, etc., are known. There are also mixed extra/intracorporal auxiliary parts, such as tooth implants, but ready-to-use prostheses for intracorporal replacement of inner organs such as the artificial heart, artificial pancreas, artificial liver or kidneys, do not yet belong to the state of the art. Basically, a technical replacement for biological parts still remains to be secured, while only partial functions can be replaced and the entire functional performance of such replaced biological parts can never be secured. In addition, the functional capacity of the technical system, in other words, of the prostheses or the artificial organ, cannot be guaranteed over a long period, and its adaptation to changing conditions is not possible as it is with a true biological part. In addition, there are significant acceptance problems, in terms of the tolerance of a foreign body in the organism and also the feeling of dependence on the function of a technical apparatus. Furthermore, the transplantation of biological parts belongs to the state of the art. In transplantation, a transfer of biological parts within the same organism (autogenic transplantation), a transfer from a donor of the same type as the receiver to said receiver (allogenic transplantation) or a transfer from a donor of a different species from the receiver to said receiver (xenogeneic transplantation) are known. The possibilities revealed by autogenic transplantation are for the most part limited by the availability of biological parts for a transfer. However, as far as is possible, it is the preferred usage, since it causes no immunological problems. Examples of this transplantation include skin transplants, the autotransfusion of blood, transplantation of muscles, fat tissue, bone, cartilage, blood vessels, etc. Because of availability, the preferred transplantation is allogenic transplantation. In this field, despite many problems involved with them, blood transfusions have succeeded in a wide range of uses, and in addition to blood banks which have been established for this purpose, now there are also skin and bone banks. Numerous other organs are likewise transplanted allogenically, such as, for instance, kidneys, hearts, livers, pancreases, bone marrow, corneas, etc. In the case of allogenic and xenogenic transplantation of biological parts however, the problem arises of immunological incompatibility, which leads to rejection by the living organism with respect to the transplant and for the most part constrains the receiver to lifelong intake of immunosuppressive substances with concurrent damaging side effects. Also, there is the continuing danger of transmission of illnesses, since the "living" biological parts cannot be sterilized. With allogenic transplantation therefore the genetic uniformity of the receiver is lost, and the transplantation itself actually becomes chimeric. In short, this object is attained by an active ingredient complex comprising a structural component, at least one recruiting component, at least one adhesion component and at least one growth and/or maturation component. With the foregoing and other objects, advantages and features of the invention that will become hereinafter apparent, the nature of the invention may be more clearly understood by reference to the following detailed description of the invention, the appended claims and to the several views illustrated in the attached drawings. The active ingredient complex according to the present invention has the quality of passing over to cells with a reciprocal reaction and inducing differentiated cell growth. For this purpose, the active ingredient complex (implant), which can also be produced on an industrial scale, is to be produced outside the body of the living organism and then brought into contact with cells which are to form the biological part. This can occur at a suitable site to which the complex is introduced, either inside the body of the living organism or, outside the body, for instance in a cell culture. In doing this, the complex according to the present invention is brought together with an accumulation of vital, function-capable and specific cells at the desired site. As is known, biological parts generally consist of specific cells and an extracellular matrix produced by the cell. Since the complex according to the present invention arranges everything for the production of the signals required for the biological part, it is now possible to hold the cells required for this purpose at the site of the complex to the desired geometry, to increase their number and to mature them with a view to the desired functions. Because the active ingredient complex for the promotion of cell growth contains the suitable relevant components for any required partial formation step, its production is guaranteed in its entirety. Furthermore, with use of the complex according to the invention, same-body cells can be used, so that the known difficulties which arise with the otherwise traditional transplantations are overcome. For example, transmission of illness is no longer possible, no long-term immunosuppression with its grave side effects is required, and the individual living organism remains a genetically uniform entity. Biological parts take up a certain amount of space for their functional performance. Frequently, their function is connected with a certain geometry within which they fulfill their function. This is also true for the biological parts produced by means of the active ingredient complex of the present invention. The active ingredient complex fulfills this function with the aid of a structural component which on the one hand exerts the space-retaining function and on the other hand allows the assumption of the existence of a geometric form within which the biological part which is produced fulfills its function. In one preferred embodiment, the active ingredient complex of the present invention is primarily a macromolecular three-dimensional matrix, which together with water and salt can be present in the form of a gel of distinct expansion properties. Thus, for instance, proteoglycan gels may form the matrix. A network of fibers, such as, for instance, different types of collagens or elastin, can also form the structural component. Likewise, combinations of gels with intercalated fibers are suitable composite materials. The structural component for the production of biological parts is manufactured differently for the different intended uses, that it can be used as a fleece, a gel or a liquid gel, which can be cut, milled, or be plastically deformed or cast. The structural component is adapted to the requirements of the biological part to be repaired or replaced since a certain specificity exists between cellular and the extracellular portions of biological parts. Sources for the production of the structural component are therefore primarily extracellular materials of different tissues or organs. For instance, for the growth of skin cells, cutaneous proteoglycan and fiber proteins are used for the production of the structural component; for the growth of spleen cells, spleen-specific proteoglycans and fibrous proteins are used; for the production of bone, bone-specific proteoglycan and fibrous proteins are used, etc. The structural component can also include metallic, ceramic, vitreous, polymeric or fatty carrier materials, to aid in the modification of the geometric, mechanical, chemical or special properties of the structural component. Thus, the carrier material together with the structural component can be present in solid, porous, membranous, micellar, viscous or liquid form according to the requirements of the particular cells which are to be grown. In another preferred embodiment of the active ingredient complex according to the present invention, the material displays its capacity for production of the biological parts, its essentially only temporarily. In other words, the active ingredient complex is configured so that it is cyclically controllably decomposable and following production of the biological part is no longer present. The rate of decomposition of the active ingredient complex can thus be controlled by different transverse cross-linking of the polymeric matrix and/or by the addition of (enzyme) inhibitors, immunosuppressants and/or inflammation-inhibiting materials. The inhibitors employed can be low-molecular compounds which occupy the active center of the decomposing enzyme or chelating agents, which bind an essential cofactor of the enzyme to themselves or to the neutralizing antibodies. Other types of inhibiting mechanisms are possible. As inflammation-inhibiting and/or immunosuppressant additives, the following can be used: inhibitors of phospholipase, such as for instance steroids; inhibitors of cyclooxygenase, such as for instance indomethacin; inhibitors of lipoxygenase, such as for instance nordihydroguaiaretic acid, immunosuppressants of the type including cyclosporin and/or of the type including antithymocytene-globulin, etc. According to this invention, living cells of the desired type are to be collected in the region of the structural component. For this purpose, the active ingredient complex further comprises one or more "recruiting components" which cause migration of the cells to the area where the biological part is desired to grow. Chemotaxins are suitable for use as a recruiting component. The chemotaxins suitable for this use have been described for a number of cells and can be isolated from human, animal, plant or microbial sources or may be produced by chemical synthesis or biotechnical methods. If the structural component produced in vitro is introduced with the recruiting component into an organism and/or is brought into contact with target cells outside the organism, it then builds a concentration gradient in which the target cells are oriented, whereby the relevant recruiting component correlates with the specific identification or recognition structures on the target cells, as receptors. When the biological part to be produced is composed of a plurality of types of cells, the structural component includes a plurality of recruiting components in the form of chemotaxins corresponding to the number of types of cells. The specificity of the relevant recruiting component for the different target cells as well as the amount of chemotaxic activity is ascertained by research, wherein the directed migration of the desired cells through defined filter pores is measured under the effect of a certain gradient of the chemotaxin in a chamber. The active ingredient system can be biologically standardized relative to its relevant recruiting component by means of researched techniques of this sort, which is important for the industrial production of the active ingredient complex. Peptides such as N-Formyl-met-leu-phe, or metabolites of arachidonic acid, such as leucotrienes (with the aid of which certain cells, or phagocytes, can be attracted out of the blood) may serve as chemotaxins. Proteins, such as those which attract mesenchyme cells, work chemotaxically especially on connective tissue cells. In addition to the specificity of the recruiting component for the desired target cells and the amount of chemotaxic activity, the time duration of the activity during which the chemotaxic concentration gradient is built up is also specific and is of considerable length. This kinetic mechanism is adapted to the requirements for the promotion of cell growth by the active ingredient complex according to the present invention by means of a controllable liberation of the relevant recruiting component from the structural component. In doing this at this point, the rate of decomposition of the structural component plays a role, as does the type of connection between the structural component and the relevant recruiting component, dependent for instance on whether there is a covalent or an associative linkage. With covalent linkage, slower synthesis and longer maintenance of the chemotaxic gradients is attained than with merely associative linkage made up of ionic forces or hydrogen bonds. The regrowth of the cells, however, for the most part, occurs more rapidly than the decomposition of the structure component, since the infused cells are quite essential for decomposition of the proteoglycan/collagen material. Following migration of the cells into the structural component, these cells must then be attached to the structural component, in order to prevent their emigration into the environment and to guarantee a stable architecture of the biological part which is produced. For this purpose, the active ingredient complex includes one or more adhesion components, by means of which the infused cells can be fixed at the site of the structural component. Thus, the adhesion components "anchor" the cells to the structural component. Such adhesions are known as having a certain anchoring specificity. Examples of adhesion components are fibronectin and laminin, which allow connective tissue or epithelial cells to be anchored to the structural component. Numerous other adhesion factors of different specificity may be used depending on the type of cells to be produced with the active ingredient complex according to the present invention. Among others, this group includes the cell adherence molecules L-CAM, N-CAM, cytotactin, tenascin, laminin, fibronectin, collagen types IV, V, VII, as well as synthetic peptides, and the partial sequences of different adhesions represent the matrix, and transmembrane protein compounds, such as for instance integrin. To increase the specificity of attachment of the desired cells to the structural component during production of the biological parts, antibodies inhibiting undesired adhesion components can be introduced. The biological activity of the adhesion components can be measured in adherence tests of various types (e.g., by means of centrifugal forces, etc.) and thus can be standardized for the entire active ingredient complex. Frequently, the cells fixed by suitable adhesions and chemotaxically attracted to the area of the structural component for production of the biological part are insufficient in number to constitute the biological part. Also, the mobile cells available in an organism for this process are found for the most part in an insufficiently mature state to fulfill all of the functions of a biological part. They frequently represent precursors or parent cells out of which the functioning mature cells of the biological part to be produced must then develop. For this purpose, the active ingredient complex, according to the invention, has at least one growth and/or maturation component, preferably in the form of one or more cytokines, under the effect of which the number of infused cells is increased and a maturation of the cells occurs. Cytokines are materials of distinct chemical structure which are characterized in that they cooperate in reciprocal reaction with cells and influence the splitting and growth of cells as well as their maturation and biosynthesis. Cytokines thus have a hormone-like effect, but do not display this quality from a distance as hormones do, but rather only in localized areas, which is advantageous in the production of biological parts, since this is a localized process. A great number of different cytokines of different specificity are known. These can be used to influence cell growth, differentiation and maturation and also to influence the metabolism of the infused cells which are introduced as other components in the active ingredient system according to the invention. The specificity of the cytokines for certain cells is determined by the presence of corresponding receptors on the target cells, whereby the interaction of a cytokine with the receptor triggers the resulting cellular reaction. The receptors on the target cells described in this case are found in membrane proteins, which pass into reciprocal reaction with the chemotaxin which is being used, link with it and invade the cell. With recycling of the receptors they are again available for linkage with chemotaxins. Analogously, with the receptors for the cytokines being introduced, it has to do only with a different specificity, while with the same reciprocal reaction mechanism. While the linkage of the chemotaxin leads to directed movement of the target cells, the linkage of the cytokines to the corresponding receptor of the target cell results in growth and/or differentiation. Frequently, the receptors are not yet characterized molecularly, so that they are known only by their specificity for the relevant ligands (chemotaxicum, cytokine, etc.). Therefore, not infrequently, stimulating or inhibiting of sequential processes can be triggered at the cells, according to the specificity of the relevant cytokine and target cells. The desired cellular reaction of the cytokine in terms of reciprocal reaction for the production of biological parts is generally connected with a dual signal transmission, so that in an advantageous manner at least two cytokines are used in the active ingredient complex according to the present invention, in order to attain both growth and differentiation. Following interaction with a cytokine, many cells produce more cytokines and release them, whereby the cells themselves can thus be stimulated or inhibited the (so-called autocrine mechanism). Frequently, the specificity of the cells for certain cytokines is modified with individual differentiation steps, so that no further interaction can occur, or the reciprocal reactions of a sequential reaction can change over from a stimulating to an inhibiting cellular reaction. The properties of a number of cytokines are known, so that the cytokine effect can likewise be standardized in the active ingredient system. Some examples of cytokines included in the production of blood, the factor stimulating colonies; in the production of connective tissue, the fibroblasts growth factor; in the production of skin, the epidermal growth factor; in the production of cartilage, the cartilage-inducing factor; in the production of spleen or lymph nodes, the lymphocytes-activating factor as well as spleen peptide; for the production of thymus, the T-cells growth factor as well as thymus peptide; for the production of bone, the bone growth factor as well as the transforming growth factor; for the production of blood vessels, the angiogenesis factor. Furthermore, the following cytokines are also used: interleukins, growth factors similar to insulin, tumor necrosis factor, prostaglandins, leukotrienes, transforming growth factors, growth factor deriving from thrombocytes, interferons, and growth factors deriving from endothelial cells. Since biological parts are composed most often of a plurality of cell types, combinations can occur. Thus, for instance, the formation of blood vessels is important for blood supply to the biological part being produced, so that accelerated vessel-formation is promoted by addition of an angiogenesis factor as cytokine component of the active ingredient system. Similarly, accelerated formation of nerve connections can be important, and can be realized by a corresponding introduction of additional cytokines into the active ingredient complex. Hereinafter the invention is to be explained in greater detail relative to two exemplary embodiments. Preparation of Active Ingredient Complex for Organogenesis of Skin Human or animal skin is disengaged mechanically from the epidermis. The cutin which is obtained is degreased in six times the amount (w:v) of chloroform/methanol 1:1, deep-frozen in liquid nitrogen and ground in a deep-freeze grinder to a particle size of 400-1000 millimicrons. The skin particles are then dried in a high vacuum (0.05 Torr) at a low temperature, suspended in a 4 M aqueous solution of guanidine chloride and stirred for 12 hours at room temperature. The undissolved portions are discarded and the dissolved portion is very thoroughly dialyzed with respect to water. The precipitated macromolecular network of proteoglycans and skin collagen is washed and dried in a high vacuum at a low temperature. The fleece which is obtained represents the structural components of the active ingredient system according to the present invention for triggering the so-called organogenesis of skin, into which are then introduced the adhesion component, the chemotaxic component (recruiting component), and the growth and maturation component (cytokine). As the adhesion component, fibronectin is worked into the structural component by precipitation, for instance by means of ethyl alcohol, out of aqueous solution and in the presence of the structural component, or else by common lyophilization. The other components are simultaneously doped into the structure component by the same method. For cutaneous organogenesis, a fibroblast growth factor (FGF) is used as well as an epidermal growth factor, in order to simplify the growth of the epidermis and the surface is provided with an additional adhesion factor, in order to simplify attachment of epithelial cells. In this embodiment, laminin is used which specifically allows for attachment of epithelial cells. The active ingredient system produced in this manner is introduced together with an immunosuppressive to promote the organogenesis of skin. Preparation of Active Ingredient for Osteogenesis Human or animal bone is disengaged from soft parts, the condyles are removed and the diaphyseal portions sawn off lengthwise and separated from the bone marrow. The bone pieces which are obtained are degreased in six time the amount (w:v) of chloroform/methanol (1:1), deep-frozen in liquid nitrogen and ground in a deep-freeze grinder down to a particle size of 400-1000 micromillimeters. The particles are demineralized in 0.5 N hydrochloric acid, then washed with water until neutralized and dried in a high vacuum at a low temperature. The bone particles are then suspended in a 4 M aqueous guanidine chloride solution and stirred for 12 hours at room temperature. The undissolved portions are discarded and the dissolved portions are thoroughly dialyzed with respect to water. The precipitated macromolecular network of proteoglycans and bone collagen is washed in water and dried in a high vacuum. The fleece which is obtained represents the structural component according to the present invention of the active ingredient system for triggering osteogenesis. An adhesion obtained from the guanidine chloride solvent fraction serves as the component, allowing for attachment of osteoblasts and their precursor cells to the structural component. The recruiting component is a protein which likewise is isolated from bone, and the active component is identified by Boyden chamber experiments. The adhesion component and the recruiting component form a chelate acting with the structural component, which carries out the attachment and settling of bone-forming cells. The chelating agent is produced by precipitation or lyophilization of the components. For dual transmission of the growth and maturation signals, basic fibroblast growth factor and transforming growth factor-beta are doped into the active ingredient complex. For reinforcement of the effect, an antibody can be added to the bone-forming active ingredient complex, acting against catabolic cytokines, such as cachexia. A suitable concentration of the cytokine is inherent in the active ingredient system, in the size range of approximately 10 ppm. Although certain presently preferred embodiments of the invention have been described herein, it will be apparent to those skilled in the art to which the invention pertains that variations and modifications of the described embodiments may be made without departing from the spirit and scope of the invention. Accordingly, it is intended that the invention be limited only to the extend required by the appended claims and the applicable rules of law. Patent Citations
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Ellis Williams Architects
Ellis Williams Architects has won a RIBA competition to design this £500,000 art and design centre for Pocklington School in East Yorkshire. The practice, designer of the acclaimed Baltic Contemporary Arts Centre in Gateshead, saw off competition from three other practices - Terry Pawson Architects, White Design and Spence Associates.The brief demanded an 'imaginative design' to engage and enthuse the pupils. The school also wanted the structure to enhance the whole campus, reflecting ...
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The redesigned 2013 Acura RDX is better armed to win over shoppers — it's larger, lighter and more efficient — while offering an attractive value proposition.
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Stewart, James B.Overview
Publication Timeline
Most widely held works about
James B Stewart
Most widely held works by
James B Stewart
Den of thieves
by James B Stewart
26 editions published between 1991 and 2010 in English and held by 3,039 WorldCat member libraries worldwide How four men--Michael Milken, Ivan Boesky, Martin Siegel, Dennis Levine--"nearly destroyed Wall Street ... how they made billions and how they got caught."
Blood sport : the president and his adversaries
by James B Stewart
21 editions published between 1995 and 1997 in English and held by 2,933 WorldCat member libraries worldwide In July 1993, White House official Vincent Foster wrote an anguished lament: "in Washington ... ruining people is considered a sport."
Blind eye : how the medical establishment let a doctor get away with murder
by James B Stewart
14 editions published between 1999 and 2007 in 3 languages and held by 2,372 WorldCat member libraries worldwide Traces the story of Michael Swango, a doctor who, the FBI believes, may be one of the most prolific serial killers in American history, discussing his checkered career and the accusations that have followed him throughout his practices in Ohio, Illinois, South Dakota, New York, and Africa
Disney war
by James B Stewart
20 editions published between 1990 and 2006 in 3 languages and held by 2,010 WorldCat member libraries worldwide Documents the fierce executive battle for control of the Walt Disney Company, in an account that discusses how Michael Eisner lost his chairmanship and how the conflict reflects modern-day American capitalism and popular culture
Heart of a soldier : a story of love, heroism, and September 11th
by James B Stewart
19 editions published between 2002 and 2009 in English and Undetermined and held by 1,557 WorldCat member libraries worldwide Relates the life of Rick Rescorla, a former soldier and the head of security for Morgan Stanley, who successfully evacuated 2,700 of the company's employees from the south tower of the World Trade Center on September 11th
Tangled webs : how false statements are undermining America : from Martha Stewart to Bernie Madoff
by James B Stewart
5 editions published between 2011 and 2014 in English and held by 1,249 WorldCat member libraries worldwide This book is the author's newsbreaking investigation of our era's most high-profile perjurers, revealing the alarming extent of this national epidemic. Our system of justice rests on a simple proposition: that witnesses will raise their hands and tell the truth. In this book he reveals in detail the consequences of the perjury epidemic that has swept our country, undermining the very foundation of our courts. With many prosecutors, investigators, and participants speaking for the first time, the book goes behind the scene of the trials of media and homemaking entrepreneur Martha Stewart; top White House political adviser Lewis "Scooter" Libby; home-run king Barry Bonds; and Wall Street money manager Bernard Madoff. The perjury outbreak is symptomatic of a broader breakdown of ethics in American life. It isn't just the judicial system that relies on an honor code: Academia, business, medicine, and government all depend on it. This book explores the age-old tensions between greed and justice, self-interest and public interest, loyalty and duty. At a time when Americans seem hungry for moral leadership and clarity, this work reaffirms the importance of truth
The partners : inside America's most powerful law firms
by James B Stewart
7 editions published between 1982 and 1984 in English and held by 1,065 WorldCat member libraries worldwide Introduces the elite corporate law firms and some of their unique contributions to economic, social, and political developments in recent years
The prosecutors : inside the offices of the government's most powerful lawyers
by James B Stewart
7 editions published between 1987 and 1988 in English and held by 898 WorldCat member libraries worldwide Goes behind the scenes of the most riveting criminal proceedings of recent years and shows a public prosecutor's work
Blind eye the terrifying story of a doctor who got away with murder
by James B Stewart
14 editions published between 1999 and 2011 in English and No Linguistic content and held by 449 WorldCat member libraries worldwide Traces the path of Michael Swango, a model young doctor whose patients from the United States to Zimbabwe began dying in suspicious circumstances and is now thought by the FBI to be the most successful serial killer in this nation's history
Managing diversity in the military : research perspectives from the Defense Equal Opportunity Management Institute
3 editions published between 2001 and 2012 in English and held by 261 WorldCat member libraries worldwide
Follow the story : how to write successful nonfiction
by James B Stewart
3 editions published in 1998 in English and held by 259 WorldCat member libraries worldwide
Blood sport [the President and his adversaries]
by James B Stewart
2 editions published in 1996 in English and held by 199 WorldCat member libraries worldwide An account of the "mysteries" of the Clinton White House
Heart of a soldier a story of love, heroism, and September 11th
by James B Stewart
5 editions published in 2002 in English and held by 194 WorldCat member libraries worldwide Rick Rescorla had led a life of adventure worthy of Kipling in such lands as colonial Africa and Vietnam, surviving battles with great courage and style. Finally settling down into a peaceful life in New York City, in charge of security for Morgan Stanley, he successfully got 2,700 of its employeees out of the World Trade Center's South Tower on September 11th. Then he went back and began climbing the tower stairs, looking for stragglers
Den of thieves
by James B Stewart
8 editions published between 1991 and 2011 in English and No Linguistic content and held by 170 WorldCat member libraries worldwide [This book] tells ... the full story of the insider-trading scandal that nearly destroyed Wall Street, the men who pulled it off, and the chase that finally brought them to justice. [The author] shows ... how four of the biggest names on Wall Street - Michael Milken, Ivan Boesky, Martin Siegel, and Dennis Levine - created the greatest insider-trading ring in financial history and almost walked away with billions, until a team of ... detectives triumphed over some of America's most expensive lawyers to bring this ... quartet to justice. Based on secret grand jury transcripts, interviews, and actual trading records, and containing ... new revelations about Michael Milken and Ivan Boesky ... [this book] weaves all the facts into a ... narrative ... of human nature, big business, and crime ... -Back cover
Disney war
by James B Stewart
8 editions published in 2005 in English and held by 139 WorldCat member libraries worldwide Once upon a time, one man ruled America's greatest entertainment company. This is the untold story of his triumphs and failures and of the revolt that cost him his kingdom
Disneywar : intrigue, treachery and deceit in the magic kingdom
by James B Stewart
1 edition published in 2005 in English and held by 38 WorldCat member libraries worldwide
Club der Diebe
by James B Stewart
5 editions published between 1992 and 1999 in German and held by 27 WorldCat member libraries worldwide
W.E.B. Du Bois on Race and Culture
by Bernard W Bell
1 edition published in 2014 in English and held by 25 WorldCat member libraries worldwide Interpreting Du Bois' thoughts on race and culture in a broadly philosophical sense, this volume assembles original essays by some of today's leading scholars in a critical dialogue on different important theoretical and practical issues that concerned him throughout his long career: the conundrum of race, the issue of gender equality, and the perplexities of pan-Africanism
Finance connection
by James B Stewart
2 editions published in 1992 in French and held by 24 WorldCat member libraries worldwide La folle aventure de quatre escrocs - Martin Siegel, Ivan F. Boesky, Michael R. Milken, Dennis B. Levine - et de tous ceux qui, par leurs manigances, ont fini par "faire sauter" la Bourse de New York
Huit jours pour sauver la finance
by James B Stewart
3 editions published in 2010 in French and held by 16 WorldCat member libraries worldwide Reconstitution du sauvetage du système financier américain, accompagné d'une galerie de portraits des grandes personnalités de la finance américaine. Cet ouvrage retrace les événements de la semaine de septembre 2008 après la faillite de la banque Lehman Brothers more
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Associated Subjects
Acheson, Dean, Armed Forces--Minorities Armed Forces--Personnel management Authorship Boesky, Ivan F Clinton, Bill, Clinton, Hillary Rodham Crime Criminal justice, Administration of Dennis, William Cullen, Disney, Roy Edward Disney, Roy O.--(Roy Oliver), Diversity in the workplace Eisner, Michael, False testimony Heroes Hudson, Manley O.--(Manley Ottmer), Hyde, Charles Cheney, Insider trading in securities Investment banking--Corrupt practices Katzenberg, Jeffrey, Law firms Law offices Law partnership Levine, Dennis, Lodge, Henry Cabot,--Jr., Management Milken, Michael New York (State)--New York Perjury Phillips, William, Physicians Police, Private Political corruption Political science Practice of law Public prosecutors Rescorla, Rick, Rescue work Reuther, Walter, September 11 Terrorist Attacks (2001) Serial murderers Serial murders Swango, Michael Truthfulness and falsehood United States Walt Disney Company Whitewater Inquiry (1993-2000) World Trade Center (New York, N.Y.) Zimbabwe
Alternative Names
Stewart, James Bennett 1952-
Стюарт, Джеймс


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We were told we needed more drama in our videos, ala Real Housewives and all that... http://youtu.be/5ME78RUjxE8 … [Read More...]
Goings On
We just got in this sitar. No price yet. (But how cool!) https://www.youtube.com/watch?v=rBhiB9extjM And as, always, please share this video, and contact us if you have furniture, clothing (or sitars!) to donate. :-) … [Read More...]
I don't buy new furniture anymore!!!
Share this video on Facebook or some other social media site and we'll give you a $10 gift certificate. * Only one gift certificate per customer. * Send us a link or screenshot as proof of the sharing. You can email us at … [Read More...]
Meredith's picks of the day
I think we're going to be making this a regular installment. Our Exec Director showing off newly donated clothes... http://youtu.be/MHyL5p0hBFo … [Read More...]


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text: The And Then There Were None! wiki last edited by kav on 08/10/13 02:47PM View full history The Legionnaires tangle with Doctor Regulus, a mad villain who harnesses the power of radioactive gold. Dr. Regulus stole the Legion of Super-Heroes clubhouse as a show of power, but eventually loses to the Legion. It is revealed that Dr. Regulus is the source behind Sun Boy receiving his power.


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When it's a must that you move your vehicle over long distances, it all comes down to timely information regarding quality service and affordable prices. According to AAA, the average cost of gas has risen forty cents compared to a month ago. As consumers, we're all trying to grapple with the continuous rise of […]
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Date: Thursday, February 5th, 2015
Time: 4:30PM – 8:00PM
Commonwealth Bar & Stage, 731 10th Ave SW
CHOA Website is not fully compatible with Internet Explorer browser.
For over 29 years the Canadian Heavy Oil Association (CHOA) has been the premier forum to obtain heavy oil and oil sands specific technical, business and industry information. The CHOA is a multi-discipline, volunteer-based, not-for-profit association focused on heavy oil and oil sands projects and developments. CHOA is not a lobby group, and is proud of its membership of individuals.
CHOA has chosen Youville Recovery Residence for Women as the charity for partnership at all the 2014 CHOA social events. Youville is honored to be invited to meet the wonderful members of CHOA and are grateful to be working with them to support this amazing program. For additional information about Youville, please take time to visit their website www.youville.net.
Technical Lunch - Facilities & Upgrading
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My meraina came out on the 12 of oct and three days later I started my period it was light and only lasted three days my bf and I are tryin to have a baby and this month my period was three days late and started as a pink and brown spotting got heavier like a normal period buh I've been getting nausia and head aches I have mood swings and a pain in my breasts with a weird feeling in my stomach my nipples also itch a lot sorry if its tmi but I took two test and both were negative just lookin for some help
Responses (3)
23 Nov 2011
suzanne is right. When I worked in Family Planning our Dr and Midwife used to have women wait for 6 months after discontinuing hormonal contraceptives before attempting to get pregnant. She would have them use a barrier method like condoms for that first 6 months to allow the hormone levels to return to normal and allow all the contraceptive to be eliminated from the body before a woman begins to try to get pregnant.
Further Information
- Mirena Information for Consumers
- Mirena Information for Healthcare Professionals (includes dosage details)
- Side Effects of Mirena (detailed)
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