- Email: [email protected]
Acute gastrointestinal bleeding, diagnosis, and treatment
October 2003
Oxidative Stress and Digestive Diseases. Edited by Toshikazu Yoshikawa. 182 pp. $128.75. S. Karger Publishers, Inc., Basel, UK, 2001. ISBN 3-8055-7230-1. Web address for ordering: www.karger.com It has become increasingly clear that oxidative stress, an imbalance between prooxidants and antioxidants, favoring the former, may play a role in initiating and mediating many diseases of the gastrointestinal tract. This book is a summary of papers given at the Symposium on Free Radicals in Digestive Diseases held in Kyoto, Japan, on October 20, 2000. The stated goal of this symposium and this book was to present “an in-depth and integrated account of the field of oxidative stress and digestive diseases.” It was therefore with great enthusiasm that this reviewer started reading this book, as a general review on this topic would be timely and a welcomed addition to the literature. It is unfortunate to state that these very broad goals of this book were not met. The book comprises 15 chapters and is organized into sections addressing general responses oxidative stress, neutrophil activation, oxidative stress in gastric mucosa, intestinal mucosa, and the hepatobiliary system, nitric oxide, and chemoprevention by antioxidants. About one-third of the chapters serve as general reviews on the topic, with the remaining articles summarizing specific experimental projects presented at the meeting. Some of the more general reviews on the issues are informative and broad, especially the series of chapters on neutrophils and their involvement in oxidative stress and diseases of the GI tract. The interest in the remaining chapters is rather “hit-or-miss” due to the specific nature of the projects being summarized. Furthermore, no attempt was made to standardize length, content, or presentation style between the chapters. The figures of one chapter in particular appear to be simple reproductions of presentation slides. In general though, the research articles are of interest to those involved in the field. Bottom Line: Although it does possess some good general reviews on the role of oxidative stress in GI diseases, this book serves mostly its original purpose, which is to summarize the proceedings of a meeting. The utility of this book as a general reference or review to the GI community as a whole is not very high.
GAVIN E. ARTEEL, Ph.D. University of Louisville Health Sciences Center Louisville, Kentucky Acute Gastrointestinal Bleeding, Diagnosis, and Treatment. Edited by Karen Kim, M.D. 288 pp. $99.50. Totowa, New Jersey, Humana Press, 2003. ISBN 1-58829-004-2. Web address for ordering: www.humanapress.com Gastrointestinal bleeding is a common clinical presentation that may result from a wide spectrum of underlying disorders.
PRINT AND MEDIA REVIEWS
1279
This book is a collection of generally excellent chapters on the multiple causes of upper and lower gastrointestinal bleeding. The goal of the book is to be a resource to both primary care physicians and gastroenterologists regarding the diagnostic and therapeutic approach to acute gastrointestinal bleeding. The book attempts to achieve this goal by providing a series of narrative reviews on the different causes of bleeding and 3 chapters on surgical and radiographic approaches to acute bleeding. A glaring omission of the text is the absence of chapters dedicated to the role of endoscopy in the diagnosis and treatment of acute gastrointestinal bleeding. While endoscopic diagnosis and therapy are discussed in a very narrow context in many of the chapters there is no global discussion of the role of endoscopy in patient triage or the selection of patients for endoscopic therapy. Endoscopic therapies are briefly discussed, as applied to specific lesion, but not discussed in the larger context of their efficacy and limitations. This piecemeal approach to endoscopy provides the reader with good understanding of the value of endoscopy in specific disease entities, but little sense of the general use of endoscopy in a patient presenting with acute gastrointestinal bleeding. There is no common editorial approach to the book. Each chapter is totally self-contained. While this allows focused discussion of each disease entity, it also results in significant overlap of chapters. Multiple chapters discuss the same topics often with contradictory statements or recommendations. For example the same potential causes of obscure bleeding are discussed in the sections on upper gastrointestinal bleeding and lower gastrointestinal bleeding. There is no common editorial template or style to give the text a coordinated or cohesive feel. The result is the feeling of reading a collection of essays on a similar topic rather than a coordinated systematic approach to gastrointestinal bleeding. The images in the book are limited to angiograms in the chapter on radiologic treatment. It is surprising that there are no endoscopic images in a textbook dedicated to lesions that are generally identified and treated using endoscopy. One of the goals of the book is to provide an evidence-based approach to the issue of acute gastrointestinal bleeding. Unfortunately, only a few chapters critically review the literature in what might be considered an evidence-based format. None of the chapters can be considered a formal systematic review with rigorous inclusion and evaluation of the existing literature. Few chapters critically appraise the validity of the papers cited or note the limitations of our current knowledge. There is little discussion of clinical outcomes beyond the cessation of the acute bleeding episode. A gastroenterologist, general practitioner, or medical student will find the book a useful resource to review information on specific causes of acute gastrointestinal bleeding, similar to what is found in a good textbook of gastroenterology. What they will not find is a critical analysis of the appropriate care of a patient with acute gastrointestinal bleeding.
1280
PRINT AND MEDIA REVIEWS
Bottom Line: Most chapters are excellent in their isolated approach to a single potential cause of bleeding, but in the end, the whole is something less than the sum of its parts.
DAVID J. BJORKMAN, M.D., M.S.P.H., S.M. (Epi) University of Utah Salt Lake City, Utah Bile Acids: From Genomics to Disease and Therapy. Edited by G. Paumgartner, D. Keppler, U. Leuschner, and A. Stiehl. 320 pp. $181.00. Kluwer Academic Publishers: the Netherlands, 2003. ISBN 0-79238-781-3. Web address for ordering: www. wkap.nl Every 2 years, since 1970, the Falk Foundation, an educational foundation sponsored by the Falk Pharma company of Freiburg, Germany, has sponsored a symposium at which the latest advances in bile acid research are presented. This volume contains the proceedings of the 17th International Bile Acid Meeting that was held in Freiburg in 2002. Molecular biology entered the bile acid field rather late, but in the past 10 years, the power of molecular biological techniques has had an enormous impact. The genes encoding the enzymes involved in bile acid biosynthesis and transport have now been cloned and knockout mice lacking these genes have been produced. In the past 5 years, the nuclear receptors involved in regulating bile acid synthesis and transport have been identified. Of these nuclear receptors, FXR appears to be the most potent, as its heterodimer with RXR regulates both bile acid synthesis and hepatocyte transport. At each symposium, the Adolf Windaus Prize, sponsored by the Falk Foundation, is awarded for outstanding bile acid research. The 2002 Windaus Prize was awarded to David Russell, of the University of Texas Southwestern in Dallas. In his prize lecture, Russell summarizes the achievements of his laboratory, which include cloning of cholesterol 7␣ hydroxylase, cholesterol 12␣ hydroxylase, and the ⌬5⫺C27 oxidoreductase. The Russell laboratory has also produced knockout mice lacking cholesterol 7␣ hydroxylase or lacking cholesterol 12␣ hydroxylase and has characterized the phenotype in collaboration with John Dietschy and Steve Turley. The Windaus lecture is followed by contributions relating to the molecular biology of bile acid biosynthesis. The laboratory of Gonzalez presents its impressive work on the generation of FXR knockout mice. Such animals are phenotypically normal, but when fed cholic acid develop fatal hepatotoxicity because of the inability of the hepatocyte to excrete the bile acid load, this in turn resulting from down-regulation of bsep, the canalicular bile salt pump. A novel finding is that FXR appears to act on the promoter of apoprotein CII, an obligate cofactor for lipoprotein lipase. The Gonzalez lab has also generated knockouts of PXR, a related nuclear receptor. PXR is involved in regulation of cyp3A, and mice lacking PXR gene function show an inability to detoxify lithocholic acid by hydroxylation.
GASTROENTEROLOGY Vol. 125, No. 4
Mangelsdorf, whose laboratory discovered that bile acids are ligands for RXR and who received the Windaus prize at the 2000 bile acid symposium, presents the intriguing hypothesis that lithocholic acid activates VDR, the vitamin D receptor. Activation of VDR leads to increased activity of cyp 3A that in turn can detoxify lithocholic acid by hydroxylation and possibly sulfation. A second mechanism by which bile acid transport and biosynthesis is regulated appears to involve components of the acute phase reaction or the inflammatory cascade. Conjugated bile acid uptake from sinusoidal plasma by the hepatocyte is mediated by ntcp, a sodium-dependent transporter. This transporter is down-regulated by endotoxemia. Work presented by the Karpen group indicates that IL-1 activates JNK, a transcription factor that in turn modulates the phosphorylation of RXR. The RXR-FXR heterodimer is considered to downregulate the synthesis of ntcp (and also bile acid biosynthesis) by inducing the synthesis of SHP, a nuclear receptor that is a general inhibitor of gene transcription. The laboratory of John Chiang continues its imaginative work on the mechanisms by which the RXR-FXR heterodimer interacts with DNA and inhibits bile acid biosynthesis. There appear to be both SHP-dependent and SHP-independent pathways for down regulation of bile acid synthesis. Additional nuclear factors such as HNF4␣ and FTF are involved, and the base sequences in DNA that bind these nuclear receptors are being identified. A key enzyme in the conversion of cholesterol to bile acid is cyp27, a mitochondrial enzyme that adds a hydroxy group to the terminal carbon of cholesterol. Dysfunction of this enzyme causes cerebrotendinous xanthomatosis, a classical Garrodian defect, in which intermediates in bile acid synthesis accumulate and are excreted in large amounts in urine and bile. Work from Pandak and Hylemon indicates that cholesterol is transported into the mitochondrion by a protein named star, and that the concentration of this protein determines the input of cholesterol into the mitochondrion; this in turns determines the rate of cholesterol 27-hydroxylation. Bile acid uptake by the hepatocyte is mediated not only by ntcp, but also by one or more sodium-independent transporters termed oatp’s (Meier group). Properties of bsep, the canalicular bile acid export pump, are being clarified. This key uphill transporter has been expressed in vesicles (Meier and Thompson groups). Dawson, who greatly advanced the bile acid field by his cloning of astp, the apical sodium-dependent transporter of the ileal enterocyte, showed that the asbt knockout mice has profound bile acid malabsorption and a 10- to 20-fold compensatory increase in bile acid biosynthesis. A new family of ATP-stimulated bile acid pumps has been identified by Sugiyami, Suzuki et al. at the University of Tokyo. These transporters (mrp3, mrp4, and possibly more mrp transporters) promote efflux of bile acids and organic anions from the cholestatic hepatocyte into sinusoidal plasma, thereby promoting renal elimination. Under physiological conditions, they may also promote bile acid transport across the basolateral membrane of cholangiocytes and ileal enterocytes. Trauner et
Oxidative Stress and Digestive Diseases. Edited by Toshikazu Yoshikawa. 182 pp. $128.75. S. Karger Publishers, Inc., Basel, UK, 2001. ISBN 3-8055-7230-1. Web address for ordering: www.karger.com It has become increasingly clear that oxidative stress, an imbalance between prooxidants and antioxidants, favoring the former, may play a role in initiating and mediating many diseases of the gastrointestinal tract. This book is a summary of papers given at the Symposium on Free Radicals in Digestive Diseases held in Kyoto, Japan, on October 20, 2000. The stated goal of this symposium and this book was to present “an in-depth and integrated account of the field of oxidative stress and digestive diseases.” It was therefore with great enthusiasm that this reviewer started reading this book, as a general review on this topic would be timely and a welcomed addition to the literature. It is unfortunate to state that these very broad goals of this book were not met. The book comprises 15 chapters and is organized into sections addressing general responses oxidative stress, neutrophil activation, oxidative stress in gastric mucosa, intestinal mucosa, and the hepatobiliary system, nitric oxide, and chemoprevention by antioxidants. About one-third of the chapters serve as general reviews on the topic, with the remaining articles summarizing specific experimental projects presented at the meeting. Some of the more general reviews on the issues are informative and broad, especially the series of chapters on neutrophils and their involvement in oxidative stress and diseases of the GI tract. The interest in the remaining chapters is rather “hit-or-miss” due to the specific nature of the projects being summarized. Furthermore, no attempt was made to standardize length, content, or presentation style between the chapters. The figures of one chapter in particular appear to be simple reproductions of presentation slides. In general though, the research articles are of interest to those involved in the field. Bottom Line: Although it does possess some good general reviews on the role of oxidative stress in GI diseases, this book serves mostly its original purpose, which is to summarize the proceedings of a meeting. The utility of this book as a general reference or review to the GI community as a whole is not very high.
GAVIN E. ARTEEL, Ph.D. University of Louisville Health Sciences Center Louisville, Kentucky Acute Gastrointestinal Bleeding, Diagnosis, and Treatment. Edited by Karen Kim, M.D. 288 pp. $99.50. Totowa, New Jersey, Humana Press, 2003. ISBN 1-58829-004-2. Web address for ordering: www.humanapress.com Gastrointestinal bleeding is a common clinical presentation that may result from a wide spectrum of underlying disorders.
PRINT AND MEDIA REVIEWS
1279
This book is a collection of generally excellent chapters on the multiple causes of upper and lower gastrointestinal bleeding. The goal of the book is to be a resource to both primary care physicians and gastroenterologists regarding the diagnostic and therapeutic approach to acute gastrointestinal bleeding. The book attempts to achieve this goal by providing a series of narrative reviews on the different causes of bleeding and 3 chapters on surgical and radiographic approaches to acute bleeding. A glaring omission of the text is the absence of chapters dedicated to the role of endoscopy in the diagnosis and treatment of acute gastrointestinal bleeding. While endoscopic diagnosis and therapy are discussed in a very narrow context in many of the chapters there is no global discussion of the role of endoscopy in patient triage or the selection of patients for endoscopic therapy. Endoscopic therapies are briefly discussed, as applied to specific lesion, but not discussed in the larger context of their efficacy and limitations. This piecemeal approach to endoscopy provides the reader with good understanding of the value of endoscopy in specific disease entities, but little sense of the general use of endoscopy in a patient presenting with acute gastrointestinal bleeding. There is no common editorial approach to the book. Each chapter is totally self-contained. While this allows focused discussion of each disease entity, it also results in significant overlap of chapters. Multiple chapters discuss the same topics often with contradictory statements or recommendations. For example the same potential causes of obscure bleeding are discussed in the sections on upper gastrointestinal bleeding and lower gastrointestinal bleeding. There is no common editorial template or style to give the text a coordinated or cohesive feel. The result is the feeling of reading a collection of essays on a similar topic rather than a coordinated systematic approach to gastrointestinal bleeding. The images in the book are limited to angiograms in the chapter on radiologic treatment. It is surprising that there are no endoscopic images in a textbook dedicated to lesions that are generally identified and treated using endoscopy. One of the goals of the book is to provide an evidence-based approach to the issue of acute gastrointestinal bleeding. Unfortunately, only a few chapters critically review the literature in what might be considered an evidence-based format. None of the chapters can be considered a formal systematic review with rigorous inclusion and evaluation of the existing literature. Few chapters critically appraise the validity of the papers cited or note the limitations of our current knowledge. There is little discussion of clinical outcomes beyond the cessation of the acute bleeding episode. A gastroenterologist, general practitioner, or medical student will find the book a useful resource to review information on specific causes of acute gastrointestinal bleeding, similar to what is found in a good textbook of gastroenterology. What they will not find is a critical analysis of the appropriate care of a patient with acute gastrointestinal bleeding.
1280
PRINT AND MEDIA REVIEWS
Bottom Line: Most chapters are excellent in their isolated approach to a single potential cause of bleeding, but in the end, the whole is something less than the sum of its parts.
DAVID J. BJORKMAN, M.D., M.S.P.H., S.M. (Epi) University of Utah Salt Lake City, Utah Bile Acids: From Genomics to Disease and Therapy. Edited by G. Paumgartner, D. Keppler, U. Leuschner, and A. Stiehl. 320 pp. $181.00. Kluwer Academic Publishers: the Netherlands, 2003. ISBN 0-79238-781-3. Web address for ordering: www. wkap.nl Every 2 years, since 1970, the Falk Foundation, an educational foundation sponsored by the Falk Pharma company of Freiburg, Germany, has sponsored a symposium at which the latest advances in bile acid research are presented. This volume contains the proceedings of the 17th International Bile Acid Meeting that was held in Freiburg in 2002. Molecular biology entered the bile acid field rather late, but in the past 10 years, the power of molecular biological techniques has had an enormous impact. The genes encoding the enzymes involved in bile acid biosynthesis and transport have now been cloned and knockout mice lacking these genes have been produced. In the past 5 years, the nuclear receptors involved in regulating bile acid synthesis and transport have been identified. Of these nuclear receptors, FXR appears to be the most potent, as its heterodimer with RXR regulates both bile acid synthesis and hepatocyte transport. At each symposium, the Adolf Windaus Prize, sponsored by the Falk Foundation, is awarded for outstanding bile acid research. The 2002 Windaus Prize was awarded to David Russell, of the University of Texas Southwestern in Dallas. In his prize lecture, Russell summarizes the achievements of his laboratory, which include cloning of cholesterol 7␣ hydroxylase, cholesterol 12␣ hydroxylase, and the ⌬5⫺C27 oxidoreductase. The Russell laboratory has also produced knockout mice lacking cholesterol 7␣ hydroxylase or lacking cholesterol 12␣ hydroxylase and has characterized the phenotype in collaboration with John Dietschy and Steve Turley. The Windaus lecture is followed by contributions relating to the molecular biology of bile acid biosynthesis. The laboratory of Gonzalez presents its impressive work on the generation of FXR knockout mice. Such animals are phenotypically normal, but when fed cholic acid develop fatal hepatotoxicity because of the inability of the hepatocyte to excrete the bile acid load, this in turn resulting from down-regulation of bsep, the canalicular bile salt pump. A novel finding is that FXR appears to act on the promoter of apoprotein CII, an obligate cofactor for lipoprotein lipase. The Gonzalez lab has also generated knockouts of PXR, a related nuclear receptor. PXR is involved in regulation of cyp3A, and mice lacking PXR gene function show an inability to detoxify lithocholic acid by hydroxylation.
GASTROENTEROLOGY Vol. 125, No. 4
Mangelsdorf, whose laboratory discovered that bile acids are ligands for RXR and who received the Windaus prize at the 2000 bile acid symposium, presents the intriguing hypothesis that lithocholic acid activates VDR, the vitamin D receptor. Activation of VDR leads to increased activity of cyp 3A that in turn can detoxify lithocholic acid by hydroxylation and possibly sulfation. A second mechanism by which bile acid transport and biosynthesis is regulated appears to involve components of the acute phase reaction or the inflammatory cascade. Conjugated bile acid uptake from sinusoidal plasma by the hepatocyte is mediated by ntcp, a sodium-dependent transporter. This transporter is down-regulated by endotoxemia. Work presented by the Karpen group indicates that IL-1 activates JNK, a transcription factor that in turn modulates the phosphorylation of RXR. The RXR-FXR heterodimer is considered to downregulate the synthesis of ntcp (and also bile acid biosynthesis) by inducing the synthesis of SHP, a nuclear receptor that is a general inhibitor of gene transcription. The laboratory of John Chiang continues its imaginative work on the mechanisms by which the RXR-FXR heterodimer interacts with DNA and inhibits bile acid biosynthesis. There appear to be both SHP-dependent and SHP-independent pathways for down regulation of bile acid synthesis. Additional nuclear factors such as HNF4␣ and FTF are involved, and the base sequences in DNA that bind these nuclear receptors are being identified. A key enzyme in the conversion of cholesterol to bile acid is cyp27, a mitochondrial enzyme that adds a hydroxy group to the terminal carbon of cholesterol. Dysfunction of this enzyme causes cerebrotendinous xanthomatosis, a classical Garrodian defect, in which intermediates in bile acid synthesis accumulate and are excreted in large amounts in urine and bile. Work from Pandak and Hylemon indicates that cholesterol is transported into the mitochondrion by a protein named star, and that the concentration of this protein determines the input of cholesterol into the mitochondrion; this in turns determines the rate of cholesterol 27-hydroxylation. Bile acid uptake by the hepatocyte is mediated not only by ntcp, but also by one or more sodium-independent transporters termed oatp’s (Meier group). Properties of bsep, the canalicular bile acid export pump, are being clarified. This key uphill transporter has been expressed in vesicles (Meier and Thompson groups). Dawson, who greatly advanced the bile acid field by his cloning of astp, the apical sodium-dependent transporter of the ileal enterocyte, showed that the asbt knockout mice has profound bile acid malabsorption and a 10- to 20-fold compensatory increase in bile acid biosynthesis. A new family of ATP-stimulated bile acid pumps has been identified by Sugiyami, Suzuki et al. at the University of Tokyo. These transporters (mrp3, mrp4, and possibly more mrp transporters) promote efflux of bile acids and organic anions from the cholestatic hepatocyte into sinusoidal plasma, thereby promoting renal elimination. Under physiological conditions, they may also promote bile acid transport across the basolateral membrane of cholangiocytes and ileal enterocytes. Trauner et