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Pharmacology of hydroxyethyl starch
21, 375-376 (1984)
CRYOBIOLOGY
BOOK REVIEW Pharmacology MISHLER
ronto,
of Hydroxyethyl IV. Oxford Univ. 1982.
Starch. By JOHN M. Press, New YorkiTo-
Uses of hydroxyethyl starch (HES) in biology, transfusion medicine, and blood banking have been reviewed in the book “Pharmacology of Hydroxyethyl Starch” by John Milton Mishler IV. His extensive research experience in the pharmacology of HES is evident in the writing and he has drawn together much information on this widely used material. The book should be welcomed by investigators in the medical community. The hydroxyethylation of starch confers increased water solubility on starch, which has found industrial applications in foods (pie filliing), pharmaceuticals (pill binders), and home products (spray starch, sizing for plaster). Mishler has dwelled on the medical applications, primarily in transfusion and experimental blood banking. There are five chapters dealing with structure and chemistry of HES, its fate in blood and tissues, pharmacokinetic effects of acute and chronic administration, and applications as a volemic colloid and in blood banking. Additionally, there are six appendixes with complete details and experimental procedures for undertaking the measurement of the chemical concentration of HES, molecular-weight and size determinations, techniques of organ perfusion, white cell isolation, and blood cell cryopreservation. These incorporate features of a technical manual and add value to the reviews and references. In the first chapter, an appreciation is given of the physical chemical properties of the different species of HES. One is made aware of the methods of manufacture and more importantly, how both molecular
weight and degree of hydroxyethyl group substitution can be manipulated to form different species. The degree of hydroxyethyl group substitution affects the manner in which the modified chains of amylopectin are catabolyzed by a-amylases in vitro and in viva. In Chapter 2 the author draws upon his own experience and that of other investigators to define the influence both of molecular weight and of degree of hydroxyethyl group substitution on the catabolism, excretion, and tissue storage of HES following administration both in animals and in man. In Chapter 3, Mishler documents the toxic effects produced by the acute and chronic administration of HES. Teratogenic effects, immunogenicity, effects on neurologic functions, rheology, and organ function, and the effects of coagulation, fibrinolysis, and hemostasis are discussed. One chapter (Chapter 4) is devoted to the experimental and clinical utilization of HES as a volemic colloid. Included in this section is a discussion of the efficacy of HES as a treatment modality in shock syndromes. Of particular interest to the readers of Cryobiology is Chapter 5 which deals with varied uses of HES both in cryobiology and in blood banking. For the cryogenic preservation of formed elements of blood, HES behaves as an extracellular cryoprotectant. When used alone, or in combination with intracellular agents such ad dimethyl sulfoxide or glycerol, HES has been relatively successful in protecting neutrophils, platelets, bone marrow, lymphocytes, and Chinese hamster cells against freeze-thaw injury. Described as promising is the full unit freezing of packed erythrocytes. Mishler postulates that after further experimental investigation, full
37.5 00 I I-2240184 $3 .OO Copyrlghf L IYX4 by Academic Prey. Inc. All nphts of reproduction in any Sbrm rcw~ved
376
BOOK REVIEW
units of HES-protected erythrocytes could be frozen, subsequently thawed, and directly administered to patients, along with the cryoprotectant HES. Thus the timeconsuming washing of cells prior to transfusion, as is now required with glycerolprotected erythrocytes, is avoided. In Appendix 6 the reader is given full details of the methods utilized in freezing full units of red cells. HES has been administered to donors to improve granulocyte yields during leukocytopheresis performed in centrifugal blood cell separators. Yields of neutrophils harvested from normal healthy donors have been enhanced some two- to threefold when HES (in conjunction with glucocorticoids) has been utilized. These concentrates of neutrophils were subsequently
used in the support of neutropenic leukemia patients undergoing chemotherapy. In addition, HES is utilized in the procurement of neutrophils by the technique of gravity leukocytopheresis, and in the preparation of leukocyte-poor blood. Appendixes 4 and 5 give experimental details of the methods for preparing neutrophils by gravity leukocytopheresis and for eliminating them in the preparation of leukocyte-poor blood. This book should be a valuable reference for investigators interested in properties and utilization of HES. Segments of the blood banking community will also find the appendixes useful. FABIAN J. LIONETTI Center for Blood Research Boston, Massachusetts 02115
CRYOBIOLOGY
BOOK REVIEW Pharmacology MISHLER
ronto,
of Hydroxyethyl IV. Oxford Univ. 1982.
Starch. By JOHN M. Press, New YorkiTo-
Uses of hydroxyethyl starch (HES) in biology, transfusion medicine, and blood banking have been reviewed in the book “Pharmacology of Hydroxyethyl Starch” by John Milton Mishler IV. His extensive research experience in the pharmacology of HES is evident in the writing and he has drawn together much information on this widely used material. The book should be welcomed by investigators in the medical community. The hydroxyethylation of starch confers increased water solubility on starch, which has found industrial applications in foods (pie filliing), pharmaceuticals (pill binders), and home products (spray starch, sizing for plaster). Mishler has dwelled on the medical applications, primarily in transfusion and experimental blood banking. There are five chapters dealing with structure and chemistry of HES, its fate in blood and tissues, pharmacokinetic effects of acute and chronic administration, and applications as a volemic colloid and in blood banking. Additionally, there are six appendixes with complete details and experimental procedures for undertaking the measurement of the chemical concentration of HES, molecular-weight and size determinations, techniques of organ perfusion, white cell isolation, and blood cell cryopreservation. These incorporate features of a technical manual and add value to the reviews and references. In the first chapter, an appreciation is given of the physical chemical properties of the different species of HES. One is made aware of the methods of manufacture and more importantly, how both molecular
weight and degree of hydroxyethyl group substitution can be manipulated to form different species. The degree of hydroxyethyl group substitution affects the manner in which the modified chains of amylopectin are catabolyzed by a-amylases in vitro and in viva. In Chapter 2 the author draws upon his own experience and that of other investigators to define the influence both of molecular weight and of degree of hydroxyethyl group substitution on the catabolism, excretion, and tissue storage of HES following administration both in animals and in man. In Chapter 3, Mishler documents the toxic effects produced by the acute and chronic administration of HES. Teratogenic effects, immunogenicity, effects on neurologic functions, rheology, and organ function, and the effects of coagulation, fibrinolysis, and hemostasis are discussed. One chapter (Chapter 4) is devoted to the experimental and clinical utilization of HES as a volemic colloid. Included in this section is a discussion of the efficacy of HES as a treatment modality in shock syndromes. Of particular interest to the readers of Cryobiology is Chapter 5 which deals with varied uses of HES both in cryobiology and in blood banking. For the cryogenic preservation of formed elements of blood, HES behaves as an extracellular cryoprotectant. When used alone, or in combination with intracellular agents such ad dimethyl sulfoxide or glycerol, HES has been relatively successful in protecting neutrophils, platelets, bone marrow, lymphocytes, and Chinese hamster cells against freeze-thaw injury. Described as promising is the full unit freezing of packed erythrocytes. Mishler postulates that after further experimental investigation, full
37.5 00 I I-2240184 $3 .OO Copyrlghf L IYX4 by Academic Prey. Inc. All nphts of reproduction in any Sbrm rcw~ved
376
BOOK REVIEW
units of HES-protected erythrocytes could be frozen, subsequently thawed, and directly administered to patients, along with the cryoprotectant HES. Thus the timeconsuming washing of cells prior to transfusion, as is now required with glycerolprotected erythrocytes, is avoided. In Appendix 6 the reader is given full details of the methods utilized in freezing full units of red cells. HES has been administered to donors to improve granulocyte yields during leukocytopheresis performed in centrifugal blood cell separators. Yields of neutrophils harvested from normal healthy donors have been enhanced some two- to threefold when HES (in conjunction with glucocorticoids) has been utilized. These concentrates of neutrophils were subsequently
used in the support of neutropenic leukemia patients undergoing chemotherapy. In addition, HES is utilized in the procurement of neutrophils by the technique of gravity leukocytopheresis, and in the preparation of leukocyte-poor blood. Appendixes 4 and 5 give experimental details of the methods for preparing neutrophils by gravity leukocytopheresis and for eliminating them in the preparation of leukocyte-poor blood. This book should be a valuable reference for investigators interested in properties and utilization of HES. Segments of the blood banking community will also find the appendixes useful. FABIAN J. LIONETTI Center for Blood Research Boston, Massachusetts 02115